T-lymphocytes cytotoxic

Restricted Cytotoxic T-Lymphocyte Responses," Biomedicine 96 Medical Research from Bench to Bedside, Washiagton, D.C., May 3—6, 1996. 

In this type of reaction an antigen elicits the generation of cytotoxic T-lymphocytes ( immune defense). Cytotoxic T-lymphocytes (Tc) destroy antigen bearing cells by inducing apoptosis. This reaction can be viewed as the cellular counterpart to the humoral Type II reactions. They play an important physiological role in the defense of viruses, and can become allergic reactions under the same conditions as described for Type II reactions. 

For the pathogenesis of multiple sklerosis, autoimmune T-lymphocy tes play a predominant role, which are directed against components of the neural myelin sheath. T-lymphocy tes by secreting cytokines such as interferon y maintain the chronic inflammation which destructs the myelin sheath. Also cytotoxic T-lymphocytes may participate directly. The cause of multiple sklerosis is unknown. Significantly increased antibody titers against several vitusses, mostly the measles virus, point to a (latent) virus infection initiating the disease. 

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. 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Otenhoff, T.H., Kale, A.B., VanEmbden, J.D.A., Thole, J.E.R., Kiessling, R. (1988). The recombinant 65-kD heat shock protein of Mycobacterium bovis bacillus calmette guerin/M. tuberculosis is a target molecule for CD4 + cytotoxic T lymphocytes that lyse human monocytes. J. Exp. Med. 168, 1947-1952. 

Rodgers KE, Leung N, Imamura T, et al. 1986. Rapid in vitro screening assay for immunotoxic effects of organophosphorus and carbamate insecticides on the generation of cytotoxic T lymphocyte responses. Pestic Biochem Physiol 26 292-301. 

Therapeutic efficacy of adoptively transferred cytotoxic T lymphocytes (CTL) has been demonstrated in clinical trials for cytomegalovirns (CMV)-associated disease (Walter et al. 1995), for EBV-associated lymphoma (Rooney et al. 1995) and nasopharyngeal carcinoma (Comoli et al. 2005) as well as for chronically active EBV infection (Savoldo et al. 2002). 

CTL Cytotoxic T lymphocyte CTLA-4 Known to be co-expressed with CD20 on activated T cells CTMC Connective tissue mast cell CVF Cobra venom factor... 

Antibodies against HCV (anti-HCV) in the blood indicate infection with the HCV. If the infection persists for more than 6 months and viral replication is confirmed by HCV RNA levels, then the person has chronic hepatitis C. Chronic disease may be due to an ineffective host immune system against the HCV. Cytotoxic T lymphocytes are ineffective in eradicating the HCV, thus allowing persistent damage to hepatic cells. Therefore, immunocompromised individuals are less likely to eliminate HCV.12... 

During the early stages of infection, approximately 10 billion viruses can be produced each day. Most of the cells containing these viruses will be lysed as a result of budding virions, killed by cytotoxic T-lymphocytes, or undergo apoptosis. However, virus will be protected within some cells, which can stay dormant for years. The initial immune response against... 

The recognition of GVT effect, which likely is caused by cytotoxic T lymphocytes in the donor stem cells, led to investigations with nonmyeloablative transplants (NMTs), in which less toxic preparative regimens are used in the hope of expanding the availability of HCT to recipients whose medical condition or age prohibits use of myeloablative regimens.4... 

Graft-versus-tumor effect Cytotoxic T lymphocytes in the donor stem cells have anti-cancer activity. 

M. Fukasawa, Y. Shimizu, K. Shikata, M. Nakata, R. Sakakibara, N. Yamamoto, M. Hatanaka, and T. Mizuochi, Liposome oligomannose-coated with neoglycolipid, a new candidate for a safe adjuvant for induction of CD8+ cytotoxic T lymphocytes, FEBS Lett., 441 (1998) 353-356. 

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

Kimura, A., Orn, A., Holmquist, G., Wizzell, H., and Ersson, B. (1979) Unique lectin-binding characteristics of cytotoxic T-lymphocytes allowing their distribution from natural killer cells and K cells. Eur. J. Immunol. 9, 575. 

These are called delayed hypersensitivity reactions since they normally occur 6-24 hours after exposure. A cell-mediated allergy involves the interaction of food allergens with sensitised lymphocytes, which usually occurs in the gastrointestinal tract. The sensitised lymphocytes produce lymphokines and the generation of cytotoxic T lymphocytes. These latter cells destroy other intestinal cells, including the epithelial cells that are critical for absorption. 

Cytotoxic T cells may play a role in inducing direct destruction of cancer cells, in particular those transformed by viral infection (and who express viral antigen on their surface). In vitro studies have shown that cytotoxic T-lymphocytes obtained from the blood of persons suffering from various cancer types are capable of destroying those cancer cells. 

IL-2-stimulated cytotoxic T cells appear even more efficacious than LAK cells in promoting tumour regression. The approach adopted here entails removal of a tumour biopsy, followed by isolation of T-lymphocytes present within the tumour. These tumour-infiltrating lymphocytes (TILs) are cytotoxic T-lymphocytes that apparently display a cell surface receptor which specifically binds the tumour antigen in question. They are thus tumour-specific cells. Further activation of these TILs by in vitro culturing in the presence of IL-2, followed by reintroduction into the patient along with IL-2, promoted partial/full tumour regression in well over 50 per cent of treated patients. 

A number of cells, including cytotoxic T lymphocytes, NK cells, and mononuclear phagocytic cells, are endowed with cytotoxic abilities and thus mediate important immunosurveillance mechanisms against neoplastic cells and viral infections. In immune-compromised hosts, a correlation has been observed between low NK cell activity and morbidity [22-25] or the incidence and severity of upper respiratory tract infections [24],... 

Abrams, J.R. et al., Blockade of T lymphocyte costimulation with Cytotoxic T Lymphocyte-associated Antigen 4-Immunoglobulin (CTL A4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells, J. Exp. Med., 192, 691, 2000. 

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