T-cell depletion

Last updated

T-cell depletion (TCD) is the process of T cell removal or reduction, which alters the immune system and its responses. Depletion can occur naturally (i.e. in HIV) or be induced for treatment purposes. TCD can reduce the risk of graft-versus-host disease (GVHD), which is a common issue in transplants. The idea that TCD of the allograft can eliminate GVHD was first introduced in 1958. [1] In humans the first TCD was performed in severe combined immunodeficiency patients. [2] [3]

Contents

Depletion methods

T cell depletion methods can be broadly categorized into either physical or immunological. Examples of physical separation include using counterflow centrifugal elutriation, fractionation on density gradients, or the differential agglutination with lectins followed by rosetting with sheep red blood cells. Immunological methods utilize antibodies, either alone, in conjunction with homologous, heterologous, or rabbit complement factors which are directed against the T cells. In addition, these techniques can be used in combinations. [4] [3]

These techniques can be performed either in vivo , ex vivo , or in vitro . [3] Ex vivo techniques enable a more accurate count of the T cells in a graft and also has the option to 'addback' a set number of T cells if necessary. Currently, ex vivo techniques most commonly employ positive or negative selection methods using immunomagnetic separation. In contrast, in-vivo TCD is performed using anti-T cell antibodies or, most recently, post-HSCT cyclophosphamide. [5]

The method by which depletion occurs can heavily affect the results. Ex vivo TCD is predominantly used in GVHD prevention, where it offers the best results. [6] However, complete TCD via ex vivo, especially in acute myeloid leukemia (AML), patients usually does not improve survival. [7] In vivo depletion often uses monoclonal antibodies (eg, alemtuzumab) or heteroantisera. [7] In haploidentical hematopoietic stem cell transplantation, in vivo TCD suppressed lymphocytes early on. However, the incidence rate of cytomegalovirus (CMV) reactivations is elevated. These problems can be overcome by combining TCD haploidentical graft with post-HSCT cyclophosphamide. [8] In contrast, both in vivo TCD with alemtuzumab and in vitro TCD with CD34+ selection performed comparably. [9]

Although TCD is beneficial to prevent GVHD there are some problems it can cause a delay in recovery of the immune system of the transplanted individual and a decreased Graft-versus-tumor effect. This problem is partially answered by more selective depletion, such as depletion of CD3+ or αβT-cell and CD19 B cell, which preserves other important cells of the immune system. [10] Another method is addition of cells back into the graft, after a comprehensive TCD method, examples are re-introduction of natural killer cells (NK), γδ T-cells [11] and T regulatory cells (Tregs). [12]

Early on it was apparent that TCD was good for preventing GVHD, but also led to increased graft rejection, this problem can be solved by transplanting more hematopoietic stem cells. This procedure is called 'megadose transplantation' and it prevents rejection because the stem cells have an ability (i.e. veto cell killing) to protect themselves from the host's immune system. [13] Experiments show that transplantation of other types of veto cells along with megadose haploidentical HSCT allows to reduce the toxicity of the conditioning regimen, which makes this treatment much safer and more applicable to many diseases. [14] [15] These veto cells can also exert graft vs tumor effect. [16]

Role in disease

In HIV

HIV has been confirmed to target CD4+ T cells and destroy them, making T cell depletion an important hallmark of HIV. [17] In comparison to HIV- individuals, CD4+ T cells proliferate at a higher rate in those who are HIV+. Apoptosis also occurs more frequently in HIV+ patients. [18]

Depletion of regulatory T cells increases immune activation. Glut1 regulation is associated with the activation of CD4+ T cells, thus its expression can be used to track the loss of CD4+ T cells during HIV. [19]

Antiretroviral therapy, the most common treatment for patients with HIV, has been shown to restore CD4+ T cell counts. [20]

The body responds to T cell depletion by producing an equal amount of T cells. However, over time, an individual's immune system can no longer continue to replace CD4+ T cells. [21] This is called the "tap and drain hypothesis."

In cancer

TCD's role in cancer increasing with the rise of immunotherapies being investigated, specifically those that target self-antigens. One example is antigen-specific CD4+ T cell tolerance, which serves as the primary mechanism restricting immunotherapeutic responses to the endogenous self antigen guanylyl cyclase c (GUCY2C) in colorectal cancer. [22] However, in some cases, selective CD4+ T cell tolerance provides a unique therapeutic opportunity to maximize self antigen-targeted immune and antitumor responses without inducing autoimmunity by incorporating self antigen-independent CD4+ T cell epitopes into cancer vaccines. [22]

In a mammary carcinoma model, depletion of CD25+ regulatory T cells increase the amount of CD8+CD11c+PD110, which target and kill the tumors. [23]

In lupus

Phenotypic and functional characteristics of regulatory T cells in lupus patients do not differ from healthy patients. However, depletion of regulatory T cells results in more intense flares of systemic lupus erythematosus. The in vivo depletion of regulatory T cells is hypothesized to occur via early apoptosis induction, which follow exposure to self Ags that arise during the flare. [24]

In murine cytomegalovirus (MCMV) infection

MCMV is a rare herpesvirus that can cause disseminated and fatal disease in the immunodeficient animals similar to the disease caused by human cytomegalovirus in immunodeficient humans. Depletion of CD8+ T cells prior to a MCMV infection effectively upregulates the antiviral activity of natural killer cells. Depletion post infection has no effect on the NK cells. [25]

In arthritis

A preliminary study of the effect on TCD in arthritis in mice models has shown that regulatory T cells play an important role in delayed-type hypersensitivity arthritis (DTHA) inflammation. This occurs by TCD inducing increased neutrofils and activity of IL-17 and RANKL. [26]

Treatment use

Haploidentical stem cell transplantation

TCD is heavily used in haploidentical stem cell transplantation (HSCT), a process in which cancer patients receive an infusion of healthy stem cells from a compatible donor to replenish their blood-forming elements. [27]

In patients with Acute Myeloid Leukemia (AML) and in their first remission, ex vivo TCD greatly reduced the incidence rate of GVHD, though survival was comparable to conventional transplants. [28]

Bone marrow transplantation

In allogeneic bone marrow transplants (BMT), the transplanted stem cells derive from the bone marrow. In cases where the donors are genetically similar, but not identical, risk of GVHD is increased. [29] The first ex vivo TCD trials used monoclonal antibodies, but still had high incidence rates of GVHD. Additional treatment using complement or immunotoxins (along with anti-T-cell antibody) improved the depletion, thus increasing the prevention of GVHD. [30] Depleting αβ T cells from the infused graft spares γδ T cells and NK cells promotes their homeostatic reconstitution, thus reducing the risk of GVHD. [31]

In vitro TCD selectively with an anti-T12 monoclonal antibody lowers the rate of acute and chronic GVHD post allogeneic BMT. Further, immune suppressive medications are usually unnecessary if CD6+ T cells are removed from the donor marrow. [32]

Patients can relapse even after a TCD allogeneic bone marrow transplant, though patients with chronic myelogenous leukemia (CML) who receive a donor lymphocyte infusion (DLI) can restore complete remission. [33]

Related Research Articles

<span class="mw-page-title-main">T cell</span> White blood cells of the immune system

T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.

Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Aplastic anemia is associated with cancer and various cancer syndromes. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

<span class="mw-page-title-main">Hematopoietic stem cell</span> Stem cells that give rise to other blood cells

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.

<span class="mw-page-title-main">Cell therapy</span> Therapy in which cellular material is injected into a patient

Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.

<span class="mw-page-title-main">Interleukin 7</span> Growth factor secreted by stromal cells in the bone marrow and thymus.

Interleukin 7 (IL-7) is a protein that in humans is encoded by the IL7 gene.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a primary immunodeficiency (PID), the immune deficiency must be inborn, not caused by secondary factors such as other disease, drug treatment, or environmental exposure to toxins. Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 430 recognized inborn errors of immunity (IEIs) as of 2019, the vast majority of which are PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, auto-inflammatory disorders, tumors, and disorders of various organs. There are currently limited treatments available for these conditions; most are specific to a particular type of PID. Research is currently evaluating the use of stem cell transplants (HSCT) and experimental gene therapies as avenues for treatment in limited subsets of PIDs.

<span class="mw-page-title-main">Minor histocompatibility antigen</span>

Minor histocompatibility antigen are peptides presented on the cellular surface of donated organs that are known to give an immunological response in some organ transplants. They cause problems of rejection less frequently than those of the major histocompatibility complex (MHC). Minor histocompatibility antigens (MiHAs) are diverse, short segments of proteins and are referred to as peptides. These peptides are normally around 9-12 amino acids in length and are bound to both the major histocompatibility complex (MHC) class I and class II proteins. Peptide sequences can differ among individuals and these differences arise from SNPs in the coding region of genes, gene deletions, frameshift mutations, or insertions. About a third of the characterized MiHAs come from the Y chromosome. Prior to becoming a short peptide sequence, the proteins expressed by these polymorphic or diverse genes need to be digested in the proteasome into shorter peptides. These endogenous or self peptides are then transported into the endoplasmic reticulum with a peptide transporter pump called TAP where they encounter and bind to the MHC class I molecule. This contrasts with MHC class II molecules's antigens which are peptides derived from phagocytosis/endocytosis and molecular degradation of non-self entities' proteins, usually by antigen-presenting cells. MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells.

<span class="mw-page-title-main">HIV/AIDS research</span> Field of immunology research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells that can be beneficial for the recipient by eliminating residual malignant cells. GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune control of hematologic malignancies. This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer. It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of alloimmunity is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect. The biology of GvT response is still not fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved. This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.

<span class="mw-page-title-main">Haematopoietic system</span>

The haematopoietic system is the system in the body involved in the creation of the cells of blood.

Marcel R.M. van den Brink is a Dutch oncologist and researcher at Memorial Sloan Kettering Cancer Center known for his research in hematopoietic stem cell transplantation for cancer patients.

Microtransplantation (MST) is an advanced technology to treat malignant hematological diseases and tumors by infusing patients with granulocyte colony-stimulating factor (G-CSF) mobilized human leukocyte antigen (HLA)-mismatched allogeneic peripheral blood stem cells following a reduced-intensity chemotherapy or targeted therapy. The term "microtransplantation" comes from its mechanism of reaching donor cell microchimerism.

Guo Mei is a hematologist and associate director of 307th Hospital of Chinese People’s Liberation Army and deputy director of Radiation Research Institute.

Thymoglobulin is an anti-human thymocyte immunoglobulin preparation made of purified polyclonal antibodies derived from rabbits. While these antibodies have a variety of specificities, their main mechanism of immunosuppression is through depletion of T cells. Thymoglobulin is currently approved for clinical use in Europe and the United States for renal allograft rejection, prevention of graft-vs.-host disease, and conditions involving bone marrow failure, including aplastic anemia and has additional off-label uses.

In the immune system, veto cells are white blood cells that have a selective immunomodulation properties. Veto cells were first described in 1979 as cells that “can prevent generation of cytotoxic lymphocytes by normal spleen cells against self-antigens”. Hence, veto cells delete T cells that recognize the veto cells.

<span class="mw-page-title-main">Shimon Slavin</span> Israeli professor of medicine

Shimon Slavin is an Israeli professor of medicine. Slavin pioneered the use of immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation for the cure of hematological malignancies and solid tumors, and using hematopoietic stem cells for induction of transplantation tolerance to bone marrow and donor allografts.

Maria Grazia Roncarolo is an Italian pediatrician who is currently George D. Smith Professor in Stem Cell and Regenerative Medicine and Professor of Medicine at Stanford University. She is also the Director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine along with Irving Weissman and Michael Longaker and the Director for Center for Definitive and Curative Medicine at Stanford.

A T memory stem cell (TSCM) is a type of long-lived memory T cell with the ability to reconstitute the full diversity of memory and effector T cell subpopulations as well as to maintain their own pool through self-renewal. TSCM represent an intermediate subset between naïve (Tn) and central memory (Tcm) T cells, expressing both naïve T cells markers, such as CD45RA+, CD45RO-, high levels of CD27, CD28, IL-7Rα (CD127), CD62L, and C-C chemokine receptor 7 (CCR7), as well as markers of memory T cells, such as CD95, CD122 (IL-2Rβ), CXCR3, LFA-1. These cells represent a small fraction of circulating T cells, approximately 2-3%. Like naïve T cells, TSCM cells are found more abundantly in lymph nodes than in the spleen or bone marrow; but in contrast to naïve T cells, TSCM cells are clonally expanded. Similarly to memory T cells, TSCM are able to rapidly proliferate and secrete pro-inflammatory cytokines in response to antigen re-exposure, but show higher proliferation potential compared with Tcm cells; their homeostatic turnover is also dependent on IL-7 and IL-15.

References

  1. ↑ UPHOFF, DE (March 1958). "Perclusion of secondary phase of irradiation syndrome by inoculation of fetal hematopoietic tissue following lethal total-body x-irradiation". Journal of the National Cancer Institute. 20 (3): 625–32. PMID   13539613.
  2. ↑ Reisner, Y; Kapoor, N; Kirkpatrick, D; Pollack, MS; Cunningham-Rundles, S; Dupont, B; Hodes, MZ; Good, RA; O'Reilly, RJ (February 1983). "Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells". Blood. 61 (2): 341–8. doi: 10.1182/blood.V61.2.341.341 . PMID   6217853.
  3. 1 2 3 Or-Geva, N; Reisner, Y (March 2016). "The evolution of T-cell depletion in haploidentical stem-cell transplantation". British Journal of Haematology. 172 (5): 667–84. doi: 10.1111/bjh.13868 . PMID   26684279.
  4. ↑ Daniele, Nicola; Scerpa, Maria; Caniglia, Maurizio; Ciammetti, Chiara; Rossi, Cecilia; Bernardo, Maria; Locatelli, Franco; Isacchi, Giancarlo; Zinno, Francesco (2012). "Overview of T-cell depletion in haploidentical stem cell transplantation". Blood Transfusion. 10 (3): 264–272. doi:10.2450/2012.0106-11. PMC   3417724 . PMID   22337272.
  5. ↑ Booth, Claire (2013). "The Current Role of T Cell Depletion in Paediatric Stem Cell Transplantation". British Journal of Haematology. 162 (2): 177–190. doi: 10.1111/bjh.12400 . PMID   23718232. S2CID   26726330.
  6. ↑ Devine, Steven; Carter, Shelly; Soiffer, Robert; Pasquini, Marcelo; Hari, Parameswaran; Stein, Anthony; Lazarus, Hillard; Linker, Charles; Stadtmauer, Edward; Alyea, Edwin; Keever-Taylor, Carolyn; O'Reilly, Richard (2012). "Low Risk of Chronic Graft Versus Host Disease and Relapse Associated with T-Cell Depleted Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia in First Remission: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0303". Biology of Blood and Marrow Transplantation. 17 (9): 1343–1351. doi:10.1016/j.bbmt.2011.02.002. PMC   3150599 . PMID   21320619.
  7. 1 2 Antin, Joseph (2011). "T-Cell Depletion in GVHD: Less is More?". Blood. 117 (23): 6061–6062. doi: 10.1182/blood-2011-04-348409 . PMID   21659553.
  8. ↑ Aversa, F; Bachar-Lustig, E; Or-Geva, N; Prezioso, L; Bonomini, S; Manfra, I; Monti, A; Schifano, C; Zlotnikov-Klionsky, Y; Martelli, MF; Sammarelli, G; Sassi, M; Soli, M; Giuliodori, S; Benecchi, M; Giuliani, N; Lohr, F; Pratissoli, S; Reisner, Y (14 November 2017). "Immune tolerance induction by nonmyeloablative haploidentical HSCT combining T-cell depletion and posttransplant cyclophosphamide". Blood Advances. 1 (24): 2166–2175. doi:10.1182/bloodadvances.2017009423. PMC   5737124 . PMID   29296864.
  9. ↑ Marek, A; Stern, M; Ansari, M; Ozsahiri, H; Güngör, T; Gerber, B; Kühne, T; Passweg, JR; Gratwohl, A; Tichelli, A; Segger, R; Schanz, U; Halter, J; Stussi, G (2014). "The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT". Bone Marrow Transplantation. 49 (1): 55–61. doi:10.1038/bmt.2013.132. PMID   24037023.
  10. ↑ Lang, P; Schumm, M; Greil, J; Bader, P; Klingebiel, T; Müller, I; Feuchtinger, T; Pfeiffer, M; Schlegel, PG; Niethammer, D; Handgretinger, R (2005). "A comparison between three graft manipulation methods for haploidentical stem cell transplantation in pediatric patients: preliminary results of a pilot study". Klinische Padiatrie. 217 (6): 334–8. doi:10.1055/s-2005-872529. PMID   16307419. S2CID   9698877.
  11. ↑ Airoldi, I; Bertaina, A; Prigione, I; Zorzoli, A; Pagliara, D; Cocco, C; Meazza, R; Loiacono, F; Lucarelli, B; Bernardo, ME; Barbarito, G; Pende, D; Moretta, A; Pistoia, V; Moretta, L; Locatelli, F (9 April 2015). "γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes". Blood. 125 (15): 2349–58. doi:10.1182/blood-2014-09-599423. PMC   4440890 . PMID   25612623.
  12. ↑ Di Ianni, M; Falzetti, F; Carotti, A; Terenzi, A; Castellino, F; Bonifacio, E; Del Papa, B; Zei, T; Ostini, RI; Cecchini, D; Aloisi, T; Perruccio, K; Ruggeri, L; Balucani, C; Pierini, A; Sportoletti, P; Aristei, C; Falini, B; Reisner, Y; Velardi, A; Aversa, F; Martelli, MF (7 April 2011). "Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation". Blood. 117 (14): 3921–8. doi: 10.1182/blood-2010-10-311894 . PMID   21292771. S2CID   206896191.
  13. ↑ Or-Geva, N; Reisner, Y (August 2014). "Megadose stem cell administration as a route to mixed chimerism". Current Opinion in Organ Transplantation. 19 (4): 334–41. doi:10.1097/MOT.0000000000000095. PMID   24905022.
  14. ↑ Ophir, E; Or-Geva, N; Gurevich, I; Tal, O; Eidelstein, Y; Shezen, E; Margalit, R; Lask, A; Shakhar, G; Hagin, D; Bachar-Lustig, E; Reich-Zeliger, S; Beilhack, A; Negrin, R; Reisner, Y (14 February 2013). "Murine anti-third-party central-memory CD8(+) T cells promote hematopoietic chimerism under mild conditioning: lymph-node sequestration and deletion of anti-donor T cells". Blood. 121 (7): 1220–8. doi:10.1182/blood-2012-07-441493. PMC   4467899 . PMID   23223359.
  15. ↑ Or-Geva, N; Reisner, Y (2015). "Exercising 'veto' power to make haploidentical hematopoietic stem cell transplantation a safe modality for induction of immune tolerance". Regenerative Medicine. 10 (3): 239–42. doi:10.2217/rme.14.94. PMID   25933232.
  16. ↑ Lask, A; Ophir, E; Or-Geva, N; Cohen-Fredarow, A; Afik, R; Eidelstein, Y; Reich-Zeliger, S; Nathansohn, B; Edinger, M; Negrin, RS; Hagin, D; Reisner, Y (11 April 2013). "A new approach for eradication of residual lymphoma cells by host nonreactive anti-third-party central memory CD8 T cells". Blood. 121 (15): 3033–40. doi:10.1182/blood-2012-06-432443. PMC   4467889 . PMID   23446736.
  17. ↑ Nishimura, Yoshiaki; Brown, Charles R.; Mattapallil, Joseph J.; Igarashi, Tatsuhiko; Buckler-White, Alicia; Lafont, Bernard A. P.; Hirsch, Vanessa M.; Roederer, Mario; Martin, Malcolm A. (2005-05-31). "Resting naïve CD4+ T cells are massively infected and eliminated by X4-tropic simian–human immunodeficiency viruses in macaques". Proceedings of the National Academy of Sciences of the United States of America. 102 (22): 8000–8005. Bibcode:2005PNAS..102.8000N. doi: 10.1073/pnas.0503233102 . ISSN   0027-8424. PMC   1142395 . PMID   15911767.
  18. ↑ Cooper, Arik; García, Mayra; Petrovas, Constantinos; Yamamoto, Takuya; Koup, Richard A.; Nabel, Gary J. (2013-06-20). "HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration". Nature. 498 (7454): 376–379. Bibcode:2013Natur.498..376C. doi:10.1038/nature12274. ISSN   1476-4687. PMID   23739328. S2CID   4331149.
  19. ↑ Palmer, Clovis; Ostrowski, Matias; Gouillou, Maelenn; Tsai, Louis; Yu, Di; Zhou, Jinglin; Henstridge, Darren; Maisa, Anna; Hearps, Anna; Lewin, Sharon; Landay, Alan; Jaworowski, Anthony; McCune, Joseph; Crowe, Suzanne (2014). "Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection". AIDS. 28 (3): 297–309. doi:10.1097/QAD.0000000000000128. PMC   4293200 . PMID   24335483.
  20. ↑ Nowak, M A; Lloyd, A L; Vasquez, G M; Wiltrout, T A; Wahl, L M; Bischofberger, N; Williams, J; Kinter, A; Fauci, A S; Hirsch, V M; Lifson, J D (October 1997). "Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection". Journal of Virology. 71 (10): 7518–7525. doi:10.1128/jvi.71.10.7518-7525.1997. ISSN   0022-538X. PMC   192098 . PMID   9311831.
  21. ↑ Ho, D. D.; Neumann, A. U.; Perelson, A. S.; Chen, W.; Leonard, J. M.; Markowitz, M. (1995-01-12). "Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection". Nature. 373 (6510): 123–126. Bibcode:1995Natur.373..123H. doi:10.1038/373123a0. ISSN   0028-0836. PMID   7816094. S2CID   4249603.
  22. 1 2 Snook, Adam; Magee, Michael; Schulz, Stephanie; Waldman, Scott (2014). "Self-tolerance eliminates CD4+ T, but not CD8+ T or B, cells corrupting cancer immunotherapy". European Journal of Immunology. 44 (7): 1956–1966. doi:10.1002/eji.201444539. PMC   4107120 . PMID   24771148.
  23. ↑ Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita; Azogui, Orly (2016). "Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells". PLOS ONE. 11 (6): e0157822. Bibcode:2016PLoSO..1157822G. doi: 10.1371/journal.pone.0157822 . PMC   4920347 . PMID   27341421.
  24. ↑ Miyara, Makoto; Amoura, Zahir; Parizot, Christophe; Badoual, Cécile; Dorgham, Karim; Trad, Salim; Nochy, Dominique; Debré, Patrice; Piette, Jean-Charles; Gorochov, Guy (2005). "Global Natural Regulatory T Cell Depletion in Active Systemic Lupus Erythematosus". Journal of Immunology. 175 (12): 8392–8400. doi: 10.4049/jimmunol.175.12.8392 . PMID   16339581.
  25. ↑ Salem, Mohamad; Hossain, Mohammad (2000). "In vivo acute depletion of CD8+ T cells before murine cytomegalovirus infection upregulated innate antiviral activity of natural killer cells". International Journal of Immunopharmacology. 22 (9): 707–718. doi:10.1016/S0192-0561(00)00033-3. PMID   10884591.
  26. ↑ Atkinson, Sara; Hoffmann, Ute; Hamann, Alf; Bach, Emil; Danneskiold-Samsøe, Niels; Kristiansen, Karsten; Serikawa, Kyle; Fox, Brian; Kruse, Kim; Haase, Claus; Skov, Søren; Nansen, Anneline (2016). "Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade". Disease Models & Mechanisms. 9 (4): 427–440. doi:10.1242/dmm.022905. PMC   4852503 . PMID   26822477.
  27. ↑ "What is Haploidentical Stem Cell Transplantation?". 2017-01-09.
  28. ↑ Ni, Xiong; Song, Qingxiao; Cassady, Kaniel; Deng, Ruishu; Jin, Hua; Zhang, Mingfeng; Dong, Haidong; Forman, Stephen; Martin, Paul; Chen, Yuan-Zhong; Wang, Jianmin; Zeng, Defu (2017). "PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells". Journal of Clinical Investigation. 127 (5): 1960–1977. doi:10.1172/JCI91138. PMC   5409099 . PMID   28414296.
  29. ↑ "Allogeneic Bone Marrow Transplant". 2021-04-07.
  30. ↑ Saad, Ayman; Lamb, Lawrence (2017). "Ex vivo T-cell depletion in allogeneic hematopoietic stem cell transplant: past, present and future". Bone Marrow Transplantation. 52 (9): 1241–1248. doi:10.1038/bmt.2017.22. PMC   5589981 . PMID   28319073.
  31. ↑ Abdelhakim, Haitham; Abdel-Azim, Hisham; Saad, Ayman (2017). "Role of αβ T Cell Depletion in Prevention of Graft versus Host Disease". Biomedicines. 5 (3): 35. doi: 10.3390/biomedicines5030035 . PMC   5618293 . PMID   28672883.
  32. ↑ Soiffer, RJ (1992). "Prevention of graft-versus-host disease by selective depletion of CD6-positive T lymphocytes from donor bone marrow". Journal of Clinical Oncology. 10 (7): 1191–1200. doi:10.1200/JCO.1992.10.7.1191. PMID   1607923.
  33. ↑ Sehn, Laurie (1999). "Comparative Outcomes of T-Cell–Depleted and Non–T-Cell–Depleted Allogeneic Bone Marrow Transplantation for Chronic Myelogenous Leukemia: Impact of Donor Lymphocyte Infusion". Journal of Clinical Oncology. 17 (2): 561–568. doi:10.1200/jco.1999.17.2.561. PMID   10080600.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.