Cytolytic lymphocytes

It is a purine antimetabolite which has marked effect on T-lymphocytes, suppresses cell mediated immunity (CMI). It selectively affects differentiation and functions of T cells and inhibits cytolytic lymphocytes. It is used primarily as immunosuppressant in organ transplantation, progressive rheumatoid arthritis and some other autoimmune diseases. 

F9. Felgar, R. E., Salhany, K. E., Macon, W. R., Pietra, G. G., and Kinney, M. C., The expression of TIA-1 + cytolytic-type granules and other cytolytic lymphocyte-associated in CD30+ anaplastic large cell lymphomas (ALCL) Correlation with morphology, immunophenotype, ultrastructure, and clinical features. Hum. Pathol. 30, 228—236 (1999). 

Tian, Q., Streuli, M., Saito, H., Schlossman, J.F. and Anderson, P. (1991). A polyadenylate binding protein localised to the granules of cytolytic lymphocytes induces DNA fiagmentation in target cells. Cell 67, 629-639. 

Gately, M.K., Wolitzky, A.G., Quinn, P.M. and Chizzonite, R, (1992). Regulation of human cytolytic lymphocyte responses by interleukin-12. Cell Immunol. 143, 127-130. 

R. Nowak, Disaster in the making. An engineered mouse vims leaves us one step away horn the ultimate bioweapon, New Scientist, 13 January 2001, 4-5 R. J. Jackson et al., Expression of mouse interleukin-4 by a recombinant ectromelia vims suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox, Journal of Virology, 75, 2001, 1205-10. 

The First Encounter with NK Cells. The NCI project site visitors arbitrarily transferred the healthy control investigator s (JGS) research funds from M.D. Anderson Hospital to the NCI intramural Herberman laboratory for the clarification of the in vitro artifact reactions . In the clarification efforts, the Herberman laboratory used the modem and accurate radioactivity-release assay , instead of the out-moded and clumsy chamber-slide assay. However the radioactivity-release assay did not distinguish between different types of cytolytic lymphocytes. Neither the HeUstrom, nor... 

Jackson RJ et al (2001) Expression of mouse interleukin-4 by a recombinant ectromeUa virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. J Virol 75 1205-10. 

Gately MK Wolilzky AG, Quinn PM, Chizzonite R. Regulation of human cytolytic lymphocyte re nses by interieukin-12. Cell Immunol 1992 143 127-142. 

Black, P.L. et al., Antitumor response to recombinant murine interferon gamma correlates with enhanced immune function of organ-associated, but not recirculating cytolytic T lymphocytes and macrophages, Cancer Immunol Immunother., 37, 299, 1993. 

Exposure of lymphocytes to authentic N=0 did not induce a global inhibition of lymphocyte function. The cytolytic activity of alloactivated mouse splenocytes as well as a murine allospecific cytolytic T lymphocyte clone were unaffected by exposure to N=0 immediately prior to the cytotoxicity assay. Additionally, the motility of various lymphocyte populations, including Con A stimulated splenocytes, alloactivated mouse splenocytes, and a T lymphocyte clone were also unaffected by previous N=0 exposure (R. A. Hoffman, J. M. Langrehr, and R. L. Simmons, unpublished observations, 1994). Thus, brief exposure to -N=0 does not affect T lymphocyte microfilament-microtubule function nor the enzymes required to induce target cell destruction. 

Bowlin, T. L., Davis, G. F., and McKown, B. J. (1988). Inhibition of alloantigen-induced cytolytic T lymphocytes in vitro with (2R, 5R)-6-heptyne-2, 5-diamine, an irreversible inhibitor of ornithine decarboxylase. Cell. Immunol. Ill, 443-450. 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

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... 

IFN-y modulates a number of components of the immune response. This is the only type II IFN whereas there are more than 20 types of type I IFNs (IFN-a, IFN-(3, IFN-w and IFN-t). It is not related to type I IFNs, has separate receptors and is encoded by a different chromosomal locus. IFN-y is produced by activated T lymphocytes (THi and CD8+ cells), NK cells, B cells, NKT cells and professional APCs. It promotes the activity of cytolytic T lymphocytes, macrophages and NK cells. The cell self-activation and activation of nearby cells in part may result from IFN-y production by professional APCs, which include monocyte/macrophage and dendritic cells. The early host defense against infection is likely to utilize IFN-y secreted by NK and professional APCs. In acquired immune responses, T lymphocytes are the major source of IFN-y. 

IFN-y is produced by THi cells and shifts the response toward a THi phenotype. This is accomplished by activation of NK cells that promotes innate immunity, augmenting specific cytolytic response and induction of macrophages. The induction of cytotoxic immunity can be direct or indirect via suppression of TH2 response. Another direct effect of IFN-y is the differentiation of naive CD4+ lymphocytes toward a THi phenotype. The cytokines present are very important in this differentiation process. Furthermore, induction of IL-12 and suppression of IL-4 by IFN result in differentiation toward a THi phenotype. 

IFN-y also induces the costimulatory molecules on the macrophages, which increases cell-mediated immunity. As a consequence, there is activation and increase in the tumoricidal and antimicrobial activity of mononuclear phagocytes, granulocytes and NK cells. The activation of neutrophils by IFN-y includes an increase in their respiratory burst. IFN-y stimulates the cytolytic activity of NK cells. It is an activator of vascular endothelial cells, promoting CD4+ T lymphocyte adhesion and morphological alterations, which facilitates lymphocyte extravasation. IFN-y promotes opsonization by stimulating the production of IgG subclasses that activate the complement pathway. A summary of the characteristics of selected cytokines is shown in Table 2.3. 

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. 

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