T-lymphocyte responses

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

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. 

Y Kawano, T Noma. Inhibition by lecithin-bound iodine (LBI) of inducible allergen-specific T lymphocytes responses in allergic diseases. Int J Immunopharmacol 18(4) 241-249, 1996. 

Pb exposure at low to moderate levels appears to alter T lymphocyte responses in such a way as to increase the risk of atopic disease and some forms of autoimmunity. Increased IgE production following exposure to Pb is among the most frequently reported immune alteration, suggesting that Pb is a possible risk factor for allergic asthma [33, 34, 40, 91, 92] as well as later life allergic disease [32],... 

Kerkvliet, N. I., Shepherd, D. M., and Baecher-Steppan, L., T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD, Toxicol. Appl. Pharmacol., 185, 146, 2002. 

The initiation and maintenance of IgE antibody responses are regulated by, and dependent upon, the generation of T lymphocyte responses of the correct (Th2-type) phenotype. These cells produce type 2 cytokines (including interleukins (IL) 4, 5, and 13) that collectively facilitate IgE antibody production, and that participate importantly in the elicitation of IgE-mediated allergic reactions [34-36],... 

Nickel salts have also been reported to have immunosuppressive properties in rodents, including giving acute thymic involution [389, 390], suppression of T lymphocyte response to T cell mitogens [389], suppression of antibody [389, 391, 392] and interferon production [393] and suppression of natural killer (NK) cell activity [389, 394-397]. 

Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP, et al Synergism of cytotoxic T lymphocyte-associated antigen-4 blockade and depletion of CD25 + regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. 

Fuel for immune cells at rest and during proliferation. Enhances T-lymphocyte responses to infection. 

Sheeja K, Kuttan G. (2007) Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide. Immunopharmacol Immunotoxicol 29 81-93. 

Rickinson AB, and Moss DJ (1997) Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection. Annu. Rev. Immunol. 15 405-431. 

Exposure of rats to carbon tetrachloride (up to 160 mg/kg/day for 10 days) by gavage did not alter the primary antibody response to sheep red blood cells, lymphoproliferative responses to mitogen or mixed leukocytes, natural killer cell activity, or cytotoxic T lymphocyte responses also, spleen and thymus weights were comparable to controls (Smialowicz et al. 1991). In rats exposed twice weekly for 4-12 weeks to 3,688 mg/kg/day, there was histologic evidence of hemorrhage, hemosiderin deposition, and lymphocyte depletion in the pancreaticoduodenal lymph node (Doi et al. 1991), an effect which may be secondary to induced hepatic damage. 

In contrast, little Is known about the molecular parameters Involved In the T-lymphocyte responses to protein antigens. The Inability to prepare T-cells of preselected specificities to desired protein regions has been responsible. In part, for our poor understanding of the T-cell responses. 

Chloroquine and hydroxychloroquine are used mainly in malaria (see Chapter 52) and in the rheumatic diseases. The mechanism of the antiinflammatory action of these drugs in rheumatic diseases is unclear. The following mechanisms have been proposed suppression of T-lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis, and the trapping of free radicals. 

Cytokines have been under clinical investigation as adjuvants to vaccines, and IFNs and IL-2 have shown some positive effects in the response of human subjects to hepatitis vaccine. IL-12 and GM-CSF have also shown adjuvant effects with vaccines. GM-CSF is of particular interest because it promotes recruitment of professional antigen-presenting cells such as the dendritic cells required for priming naive antigen-specific T-lymphocyte responses. There are some claims that GM-CSF can itself stimulate an antitumor immune response, resulting in tumor regression in melanoma and prostate cancer. 

Le Gal, F.A., Prevost-Blondel, A., Lengagne, R., et al. (2002) Lipopeptide-based melanoma cancer vaccine induced a strong MART-27-35-cytotoxic T lymphocyte response in a preclinal study. Int. J. Cancer 98(2), 221-227. 

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. 

In summary, chemical sensitization is dependent upon intact immunological function and the integrity of T lymphocyte responses. It is also dependent upon the ability of the hapten-protein complex to stimulate (in a susceptible individual) an immune response of sufficient vigor and of the right quality such that when that individual is exposed to the inducing chemical for the second time (by an appropriate route) they will mount a more accelerated and more aggressive inflammatory response. 

HBV is not directly cytopathic instead liver injury is immune related, and T lymphocytes are important for both the host cellular and humoral responses. Recovery from acute HBV infection depends on both B-cell and T-ceU responses. B-cell-dependent antibodies are produced to presurface and surface antigens. Cytotoxic T lymphocyte response is mounted against multiple epitopes in the HBV envelope, nucleocapsid, and polymerase regions. Cytotoxic T lymphocyte-mediated lysis of infected hepatic cells occurs, resulting in liver injury. Immune clearance of virus is often accompanied by worsening liver disease, known as a flare. An extreme example of this is seen in fulminant hepatitis B, when there is often no evidence... 

To fuUy activate the CD8+ cytotoxic T-lymphocyte requires CD4+ T-lymphocyte activation, namely, the THi subset, and its subsequent secretion of IL-2 (Eig. 84-4A). This model of CD8+ cytotoxic T-lymphocyte activation requires the close proximity of two rare- antigen-specific T-lymphocytes. In addition, some CD8+ cytotoxic T-lymphocyte responses can occur in the absence of CD4+ T-lymphocytes. New data suggest that CD4+ T-lymphocytes can ac-tivate/prime APCs through CD40. This interaction primes the APC (e.g., dendritic cell) to fuUy activate CD8+ cytotoxic T-lymphocytes (see Pig. 84-4S). It is important to remember that the classification of CD4+ lymphocytes as T-helper lymphocytes and CD8+ lymphocytes as T-cytotoxic lymphocytes is not an absolute. Some CD8+ T-lymphocytes secrete cytokines similar to a T-helper lymphocyte, and some CD4+ T-lymphocytes can act as cytotoxic cells. 

Antonen, J. et al. (1996) Intravenous caldtriol therapy restores reduced antigen-induced T-lymphocyte response in l,25-(OH)2D3-defident hemodialysis patients. Nephron, 74, 680-686. 

Figure 5.1 The influence of cytokines on the development of divergent CD4+ (Th1 and Th2) and CD8+ (Tc1 and Tc2) T-lymphocyte responses.

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