Lymphocyt specific, cytotoxic

Azathioprine, cyclophosphamide, methotrexate, leflunomide Lymphocyte-specific cytotoxic agents Mycophenolate mofetil... 

Unlike these nonspecific agents, mycophenolate mofetil (6.4) tends to be a lymphocyte-specific cytotoxic agent. Mycophenolate mofetil is a semisynthetic derivative of mycophe-nolic acid, isolated from the mold Penicillium glaucum. It inhibits both T and B lymphocyte action. Since it inhibits the enzyme inosine monophosphate dehydrogenase, which catalyses purine synthesis in lymphocytes, this agent has a more specific effect on lymphocytes than on other cell types. Mizoribine (6.5) is a closely related drug which inhibits nucleotide synthesis, preferentially in lymphocytes. 

CpG ODNs are also effective as vaccine adjuvants to enhance adaptive TH1 cellular immune responses.104 In mice, CpG ODNs can trigger strong TH1 responses,105 enhancing the number and function of tumor-specific Cytotoxic T lymphocytes (CTLs) and IFN-y secreting T cells.106 This has resulted in therapeutic vaccines in mouse tumor models where no other approach has shown comparable efficacy, even with large (1 cm) established tumors.107 108 Even without a vaccine, CpG ODNs can induce CD8+ T cell-mediated regression of established tumors with durable memory responses.109... 

The stress-associated shift in Thl/Th2 cytokines observed in human subjects has also been demonstrated in restraint-stressed mice. Associated with the shift towards a Th2 response are a significant decrease in NK cell activity, decreased IFN-y production by Con A-stimulated splenocytes, and a concomitant increase in serum corticosterone levels after 24 hours of restraint.30 These observations are consistent with studies on the effects of restraint stress and the immune response to viral infection. Restraint-stressed mice exhibited a decline in NK cell activity and a decrease in the generation of virus-specific cytotoxic T lymphocytes to HSV-l after primary infection, which resulted in an increase in the replication of the virus at the site of infection.3132... 

Bonneau, R. H. et al., Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection, Brain Behav. Immun., 5, 170, 1991. 

Ehrlich, J.P., Gunnison, A.F., and Burleson, G.R. 1989. Influenza virus-specific cytotoxic T-lymphocyte activity in Fischer 344 rat lungs as a method to assess pulmonary immunocompetence Effect of phosgene inhalation. Inhalation Toxicol. 1 129—138. 

Byrne, J.A. and Oldstone, M.B., Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus clearance of virus in vivo, /. Virol., 51, 682-686,1984. 

Figure 5 Relative amount of circulating TRP2 specific cytotoxic T-lymphocytes in the blood of mice. After three rounds of vaccination with the indicated formulations blood was collected and TRP2-specific CD8+ T cells were quantified by TRP2-loaded DimerX by FACS analysis. SIINFEKL-loaded DimerX used as control was a background level (data not shown).

M. Theobald, T. Rnppert, U. Kuckelkorn, J. Hernandez, A. Hanssler, E.A. Ferreira, U. Liewer, J. Biggs, A.J. Levine, C. Huber, U.H. Koszinowski, P.M. Kloetzel, and L.A. Sherman, The sequence alteration associated with a mntational hotspot in p53 protects cells from lysis by cytotoxic T lymphocytes specific for a flanking peptide epitope, J. Exp. Med. 188, 1017 1028 (1998). 

J. Kuball, M. Schnler, E. Antunes-Ferreira, W. Herr, M. Neumann, E. Obenaner-Kntner, E. Westreich, C. Huber, T. Wolfel, and M. Theobald, Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector based vaccination in mice bnt not man. Gene Therapy, 833-843 (2002). 

Mechanism of Action Abiologic response modifier that inhibits viral replication in virus-infected cells, suppresses cell proliferation, increases phagocytic action of macrophages, and augments specific cytotoxicity of lymphocytes for target cells. Therapeutic Effect Inhibits viral growth in condylomata acuminata. 

Koyama, T., Hall, L. R., Haser, W. G., Tonegawa, S., and Saito, H. (1987). Structure of a cytotoxic T-lymphocyte-specific gene shows a strong homology to fibrinogen beta and gamma chains. Proc. Natl. Acad. Set. USA 84, 1609-1613. 

Iwasaki, A., Dela Cruz, C.S., Young, A.R. and Barber, B.H. (1999) Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization. Vaccine, 17, 2081-2088. 

Cellular responses, as measured by a mixed-lymphocyte reaction, cytotoxic T lymphocyte response, and NK cell activity, were all undiminished, and if anything, there was a slight increase in CTL and NK responses. As would be expected by the histologic profile and the known increases in cytokine and chemokine production associated with the administration of PS ODNs in rodents, in this series of experiments there was no diminution in immune response. Administering a mouse-specific ICAM-1 inhibitor produced reductions in mixed lymphocyte reactions. This inhibition was expected as this is one of the desired pharmacologic effects of reducing ICAM-1 expression. 

T lymphocytes, thymus-derived lymphocytes or T cells are formed in the thymus. They carry out immune reactions involving cell-cell interactions and are responsible for cell-mediated immunity. One distinguishes specific and non-specific cytotoxic killer T cells, (NK cells, natural killer cells), and helper T cells which cooperate with antigen-presenting cells, APC s, in the initiation of an immune response. Suppressor T cells dampen the action of helper T cells. 

Not all T cells are cytotoxic. Helper T cells, a different class, stimulate the pro-liferation of specific B lymphocytes and cytotoxic T cells and thereby serve as partners in determining the immune responses that are produced. The importance of helper T cells is graphically revealed hy the devastation wrought hy AIDS, a condition that destroys these cells. 

Jacobson S, Shida H, McFarlin DE, Fauci AS, Koenig S (1990) Circuladng CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in padents widi HTLV-I associated neurological disease. Nature 348 245-248. 

Pai ker CE, Daenke S, Nightingale S, Bangliam CR (1992) Activated, HTLV-1-specific cytotoxic T-lymphocytes aie found in healtliy seroposidves as well as in padents widi ti opical spasdc pai apaie-sis. Virology 188 628-636. 

Lukacher, A.E., Braciale, V.L. and Braciale, T.J. (1984). In vivo effector function of influenza virus-specific cytotoxic T-lymphocyte clones is highly specific. J. Exp. Med. 160, 814-826. 

Rock, K.L., Rothstein, L., Fleishacker, C. and Gamble, S. (1992). Inhibition of class I and class II MHC-restricted antigen presentation by cytotoxic T lymphocytes specific for an exogenous antigen. J. Immunol. 148, 3028-3033. 

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