Cytolytic T cells

Wagner L, Yang OO, Garcia-Zepeda EA, et al. Beta-chemokines are released from HIV-l-specihc cytolytic T-cell granules complexed to proteoglycans. Nature 1998 391(6670) 908-911. 

Antigen MHC class I complexes have a different function and present their antigen to CD8+ cytolytic T cells, which produce an appropriate group of effector molecules leading to apoptosis of target cells. 

Both the B cells and T cells arise in the fetal liver or bone marrow (Fig. 31-1) from pluripotent stem cells. In birds the B cells develop in a special organ, the bursa of Fabricius. Mammalian B cells complete their differentiation into mature lymphocytes within the bone marrow. However, the T cells must travel to the thymus, where they complete their maturation. The T lymphocytes include the previously mentioned NK cells as well as the somewhat similar cytolytic T cells and immunoregulatory T cells. The latter are further characterized as helper T cells41 or suppressor T cells. The adaptive response requires cooperation of helper T cells in many instances. Tire mature B and T cells leave the bone marrow and thymus, which are known as the primary lymphoid tissues, and enter the blood circulation. Following "homing" signals42 they take up residence in a variety of locations... 

Figure 32-4 Sketch illustrating only a few of the many aspects of apoptosis in a mammalian cell. Emphasis here is on the death receptor pathways and cytochrome c-activated apoptosis. A third pathway is initiated by stress in endoplasmic reticulum membranes. In addition, attack by cytolytic T cells sometimes causes apoptosis by action of a granzyme on protein Bid or via a death receptor. Objects in scheme are not drawn to a single scale.

HIV is a retrovirus that infects CD4+ cells. After HIV becomes integrated into the genome of the CD4+ cells, activation of these cells results in the replication of virus, which causes lysis of the host cells. Patients infected with HIV, and with AIDS, generally have reduced numbers of helper T cells and the CD4 CD8 ratio may be as low as 0.5 1 instead of the normal 2 1. As a consequence, very little IL-2 is available to support the growth and proliferation of CD4+ cells despite the presence of effector cells, B cells and cytolytic T cells. 

Glucocorticoids inhibit acquired or cell-mediated immunity. Their effects are mediated via inhibition of genes that code for various cytokines. The cytokines inhibited by glucocorticoids include IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and IFN-y. IL-2 inhibition by corticosteroids is the most crucial effect in immunosuppression, which results in the inhibition of T-cell proliferation and activation of cytolytic T cells. Glucocorticoids also slightly affect humoral immunity by inhibiting B-cell clonal expansion and antibody synthesis, and these effects are mediated via their ability to inhibit B cells ability to express IL-2 and IL-2 receptors. 

Acute cellular rejection involves infiltration of macrophages and lymphocytes into the graft and is evident from the necrosis of the parenchymal cells of the graft. The lysis of the parenchymal cells of the transplanted tissue is achieved by the infiltrating leukocytes. Acute cellular rejection may be the product of several mechanisms including cytolytic T-cell-mediated lysis, NK cell-mediated lysis and activated macrophage-mediated lysis. The acute cellular rejection predominantly involves CD8+ T cytolytic cells that kill the grafted tissue. 

B. Lowin, M. Hahne, C. Mattmann, and J. Tschopp. 1994. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways Nature 370 650-652. (PubMed)... 

Liver injury is immune mediated with cytolytic T cells maintaining the primary role in cell destruction. Death of hepatocytes results in viral elimination and eventual resolution of the clinical illness. Viremia begins soon after infection and continues throughout the time liver enzymes are elevated. The host antibody response to HAV initially appears as the viral particles begin to disappear from stool. Like most host antibody responses, antibodies of the IgM class appear first and imply recent infection. IgM anti-HAV usually is detectable 5 to 10 days before symptoms appear. After 2 to 6 months, the IgM antibodies are replaced with IgG antibodies, which usually persist throughout life and confer immunity to HAV. Patients who receive immunoglobulin will have low titers of anti-HAV for several weeks after inoculation. Patients who receive hepatitis A vaccine will also have anti-HAV. ... 

Biological Activities of IL-2. The most commonly used vitro biological assay for IL-2 is the stimulation of IL-2-dependent T cells to proliferate. Incorporation of tritiated thymidine ( H-Tdr) by an IL-2-dependent, cloned murine cytolytic T-cell line (CTLL) is used as a measure of proliferation and is related to the amount of IL-2 present in the sample compared to that incorporated by a standard. Due to laboratory variations in the IL-2 standard used (no international IL-2... 

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