T lymphocytes depletion

Karlsson GB, Halloran M, Schenten D, Lee J, Racz P, Tenner-Racz K, Manola J, Gelman R, Etemad-Moghadam B, Desjardins E, Wyatt R, Gerard NP, Marcon L, Margolin D, Fanton J, Axthelm MK, Letvin NL, Sodroski J (1998) The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian- human immunodeficiency virus-infected macaques. J Exp Med 188 1159-1171... 

Early neuronal damage detected by immunohistochemistry has been confirmed by brain magnetic resonance spectroscopy (MRS) analysis of the neuronal marker N-acetylaspartate (NAA) (commonly expressed as an NAA/creatine ratio NAA/ Cr) in the acute and chronic phases of infection in SIV-infected macaques (Fuller et al. 2004 Greco et al. 2004 Lentz et al. 2005 Lentz et al. 2008 Williams et al. 2005). In a macaque model involving CD8h- T lymphocyte depletion along with SIV inoculation, Williams et al. (2005) demonstrated a reduction in NAA/Cr in the... 

Gradual diminution of 004 T-lymphocytes from the peripheral blood is the most consistent feature observed in HIV infection. Because the majority of 004 cells are T-helper lymphocytes, removal leads to deficiency of cellular immunity, which depends on T-helper cells to initiate cytotoxic T-ceU killing of vims-infected cells of cancer. The loss of immune surveillance leads to the appearance of viraHy induced tumors from unopposed clonal expansion of viraHy transformed cells. Furthermore, depletion of cellular immunity leads to exaggerated viral, fungal, and proto2oal infections. 

Inhibition of immunomodulatory cytokines (Fig. 1) Anti-T-cell receptor antibodies Muromonab (OKT3, Orthoclone ) binds to the CD3 complex of the T-cell receptor and induces depletion of T-lymphocytes. It is applied to prevent acute rejection of kidney, liver, and heart allografts. Rapid side effects (within 30-60 min) include a cytokine release syndrome with fever, flu-like symptoms, and shock. Late side effects include an increased risk of viral and bacterial infections and an increased incidence of lymphproliferative diseases due to immunosuppression. 

Human immunodeficiency virus (HIV) Differs from other retroviruses in that the core is cone-shaped rather than icosahedral HIV is transmitted from person to person via blood or genital secretions. The principal target for the virus is the CD4+ T-lymphocyte cells. Depletion of these cells induces immunodeficiency... 

It has been estimated that 1-2 per cent of the US population suffer from autoimmune conditions, including rheumatoid arthritis, MS and some forms of diabetes. In many instances, an autoimmune response results from the inappropriate activation of a specific subset of B- and/or T-lymphocytes. The most common immunotherapeutic approach to potentially treat such diseases is to induce depletion of the individual s T- and B-cell populations. This could be achieved by administration of an antibody raised against a surface antigen present on such cells. Initial trials, for example, have shown that injection of an (unconjugated) anti-CD4 antibody (cell surface glycoprotein present on many T-lymphocytes) over 7 days significantly reduced the clinical symptoms of rheumatoid arthritis for several months. 

After this initial phase of infection subsides, the free viral load in the blood declines, often to almost undetectable levels. This latent phase may last for anything up to 10 years or more. During this phase, however, there does seem to be continuous synthesis and destruction of viral particles. This is accompanied by a high turnover rate of (CD4+) T-helper lymphocytes. The levels of these T-lymphocytes decline with time, as does antibody levels specific for viral proteins. The circulating viral load often increases as a result, and the depletion of T-helper cells compromises general immune function. As the immune system fails, classical symptoms of AIDS-related complex (ARC) and, finally, full-blown AIDS begin to develop. 

Cells other than T lymphocytes also appear to be involved in tolerance induction. Depletion of macrophages inhibited tolerance induction and transfer studies with non-T cell fractions from tolerant animals was shown to confer tolerance to naive animals [29] Thus, tolerance induction by low doses of D-penicillamine appears to have a complex mechanism that includes various T cell subsets as well as non-T cells, that may be antigen presenting cells. 

HIV-1 is the etiologic agent responsible for AIDS, a syndrome characterized by depletion of CD4+ T-lymphocytes and collapse of the immune system. People with AIDS are prone to opportunistic infections easily defended against by a normal immune system. Generally, it takes several years, post-infection, to progress to AIDS. 

Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP, et al Synergism of cytotoxic T lymphocyte-associated antigen-4 blockade and depletion of CD25 + regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. 

Exposure of rats to carbon tetrachloride (up to 160 mg/kg/day for 10 days) by gavage did not alter the primary antibody response to sheep red blood cells, lymphoproliferative responses to mitogen or mixed leukocytes, natural killer cell activity, or cytotoxic T lymphocyte responses also, spleen and thymus weights were comparable to controls (Smialowicz et al. 1991). In rats exposed twice weekly for 4-12 weeks to 3,688 mg/kg/day, there was histologic evidence of hemorrhage, hemosiderin deposition, and lymphocyte depletion in the pancreaticoduodenal lymph node (Doi et al. 1991), an effect which may be secondary to induced hepatic damage. 

Rituximab is a chimeric monoclonal antibody that targets CD20 lymphocytes (see Chapter 55). This depletion takes place through cell-mediated and complement-dependent cytotoxicity and stimulation of cell apoptosis. Depletion of lymphocytes reduces inflammation by decreasing the presentation of antigens to T lymphocytes and inhibiting the secretion of proinflammatory cytokines. Rituximab rapidly depletes peripheral cells although this depletion neither correlates with efficacy nor with toxicity. 

Mechanism of Action Antibodies of multiple specificities interact with lymphocyte surface antigens, depleting numbers of circulating T-lymphocytes and modulating T-lymphocyte activation, homing and cytotoxic processes... 

Some chemicals can affect other parts of the immune system. For example, polychlorinated hydrocarbons such as dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs) damage the thymus, which is a lymphoid organ, producing mature T lymphocytes from the precursor cells, which are produced in the bone marrow. The result is depletion of the T cells in the thymus. 

Although this chapter will only discuss IMS in relation to cell-sorting, this approach has also been adapted for DNA sequencing (1), purification of DNA binding proteins (2), immobilization and isolation of nucleic acids (3), tissuetyping (4,5), quantification of lymphocyte subsets directly from blood (6), bone marrow T-cell depletion (7), depletion of malignant neuroblastoma cells from... 

Bishop DK, Li W, Chan SY, Ensley RD, et al. 1994. Helper T lymphocytes unresponsiveness to cardiac allografts following transient depletion of CD4-positive cells. Implications for cellular and humoral responses. Transplantation. 58 576-584. 

CDw52, a 21- to 28-kDa phosphatidylinositol-linked glycoprotein of unclear function, is widely expressed on the cell surface of both B and T lymphocytes (187). Anti-CDw52 mAbs include CAMPATH-1 and its humanized version CAMPATH-1H (187-188). CAMPATH-IH has been evaluated in multiple clinical trials, in which it has shown anticancer efficacy against a variety of lymphoid neoplasms (188-190). However, CAMPATH-IH also induced rapid depletion of both B cells and T cells, resulting in potentially profound immunosuppression (191). 

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