Helper T-lymphocyte

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. 

Autoimmune Disease. Figure 1 Mechanisms of self tolerance. DC, dendritic (antigen presenting) cell T, T-lymphocyte Th, T helper lymphocyte Treg, T regulatory lymphocyte. For details see text. 

This class of lymphocytes differentiates from immuno-logically incompetent hematopoietic stem cells of the bone marrow within the thymus - hence, the name thymus-dependent (T-) lymphocytes. Two major subclasses develop simultaneously, T-helper lymphocytes (Th) and cytotoxic effector lymphocytes (Tc). The cytotoxic T-lymphocytes (carrying on the surface the differentiation marker CD8) destroy cells, which cany their cognate antigen bound to MHC class I molecules on the surface by inducing apoptosis. From an evolutionary point of view Tc cells appear to have developed predominantly to cope with vims infections. As vituses can only replicate within cells, Tc eliminate them by destroying their producers. 

Immune Defense. Figure 2 Cytokines involved in the development of adaptive immune responses in secondary lympoid tissues such as the lymph nodes or spleen. Abbreviations B B-lymphocyte, IFN interferon, Ig immunoglobulin, IL interleukin, NK natural killer cell, TE T-effector (cytotoxic) lymphocyte, TH T-helper lymphocyte... 

Murine monoclonal antibodies reacting with CD4, which is solely located on T-helper lymphocytes and monocytes/macrophages, may also be suited for immunosuppression. 

Lloyd CM, Delaney T, Nguyen T, et al. CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo. J Exp Med 2000 191(2) 265-274. 

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. 

HIV infects and destroys T-helper lymphocytes, i.e. it directly attacks an essential component of the immune system itself. 

Mercuric chloride was then tested on human thymocytes and peripheral blood lymphocytes, fractionated according to density [161], and it seemed possible that mercuric chloride was a polyclonal stimulator of human peripheral blood T helper lymphocytes and thymocytes with characteristics of medullary cells. When macrophages were depleted, the stimulation remained at about the... 

Recently, it has been possible to grow cells of the human immune system in special mice. These mice carry a genetic defect called severe combined immunodeficiency (SCID), which leaves them with crippled immune systems, much like those in AIDS patients. Because SCID mice lack functional cellular immunity, it is possible to implant them with human cells without tissue rejection taking place. Researchers have recently developed techniques to implant human fetal tissues containing stem cells for the blood into SCID mice. It is then possible to reconstitute these mice with functional human immune system cells, including T lymphocytes and B lymphocytes. They have also found that if these SCID mice are infected by HIV, the virus will establish infection in the human tissue and destroy the T helper lymphocytes, just as it does in humans. Thus, it may be possible to study some of the mechanisms by which HIV attacks the immune system in these mice. In addition, they may be very useful for testing potential antiviral drugs. 

DeBell, K. E., Conti, A., Alava, M. A., Hoffman, T., and Bonvini, E. (1992) Microfilament assembly modulates phospholipase C-mediated signal transduction by the TCR/CD3 in murine T helper lymphocytes. J. Immunol. 149,2271-2280. 

AIDS, caused by the human immunodeficiency virus (HIV), represents the most dramatic example of viral-induced cell depletion (A6). The FasL of T cells in AIDS patients is upregulated by two HIV gene products Tat and gpl20 for the depletion of CD4 T helper lymphocytes (A6). Tat is secreted by HIV-infected cells and can penetrate noninfected T cells to upregulate FasL expression in the affected cells and may thus facilitate Fas-mediated apoptosis. In addition, gpl20 can sensitize T cells for CD95-mediated apoptosis (A6). 

T-helper lymphocytes Blood monocytes Tissue macrophages... 

Shizuru, J. A., Taylor-Edwards, C., Banks, B. A., Gregory, A. K., and Fathman, C. G. (1988). Immunotherapy of the nonobese diabetic mouse Treatment with an antibody to T-helper lymphocytes. Science 240, 659-662. 

HIV is a member of the retrovirus family (see Table 34-1).32 HIV impairs the function of certain cells in the immune system such as CD4+ (T-helper) lymphocytes.11,26 Destruction of immune system components often leads to the severe immunocompromised state known as AIDS. This virus exists in at least two forms HIV-1 and HIV-2. Both forms of the virus are capable of causing AIDS, but HIV-1 is more prevalent.32 Hence, HIV-1 is also referred to informally as the AIDS virus. Because there is currently no effective way to kill the AIDS virus in humans, there is no cure for AIDS. 

Immune synapses in the CNS are MHC-II-expressing microglia interacting with T-helper lymphocytes. 

Glimcher LH, Murphy KM Lineage commitment in the immune system the T helper lymphocyte grows up. Genes Dev. 2000 14 1693-711. 

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