Date of Award

1993

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Veterinary Medical Sciences - Comparative Biomedical Sciences

First Advisor

David W. Horohov

Abstract

Generation of an optimal immune response against a pathogen leads to protection from disease. Cytokines orchestrate a complex but well coordinated interaction between the cells of the immune system. Precise and sequential signals are required for the induction of a particular cellular function. In this study, I have analyzed the minimal signal requirement for memory cytotoxic T lymphocyte (mCTL) effector function. I have used human peripheral blood T cells as the source of influenza virus specific mCTL precursors, and influenza virus infected and formaldehyde fixed cells as antigen presenters in our assay system. Using this model, we have identified an essential requirement for antigenic restimulation in influenza virus specific mCTL induction. Further I show here, using known recombinant cytokines, that IL-4, IL-7, IL-10 and IL-12 can function as CTL differentiation factors. Unlike many previous reports, in our assay system, we did not find any direct cytotoxicity induction by IL-2, but it has modulatory role on IL-7, IL-10 and IL-12 mediated induction of cytotoxicity. In contrast to IL-2, IL-4 has both positive and negative regulatory effects on cytotoxicity induction and depends critically on the time of addition of cytokines after antigen encounter.

Pages

89

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