CD4 T lymphocytes initiate most specific immune responses. These responses can take two main forms, humoral immunity and cell-mediated immunity. In the former, CD4 T cells activate B cells to secrete immunoglobulin particularly of the IgG1, IgA, and IgE isotypes, while in the latter CD4 T cells activate macrophages. These different effector mechanisms are induced in response to different types of antigen or pathogens. Data obtained using cloned murine and human CD4 T cells suggest that these two types of response reflect the activation of functionally distinct sets of CD4 T cells that secrete distinct cytokines, with the release of IL-4 and IL-5 being associated with the elicitation of humoral immunity and the release of IFNgamma and lymphotoxin being associated with cell mediated immunity. These findings have been extended in vivo with the analysis of cytokine release following various parasitic infections. How the immune system regulates which subset of CD4 T cell to activate is the focus of this application. The overall goal is to define those factors which control the selective activation f one CD4 T cells subset over the other. We will test the role of 4 elements in the differential priming of CD4 T cell subsets. These are: the role of ligand density, the role of T cell receptor interaction with its ligand, the role of the antigen presenting cell type and the role of the cytokine environment during priming. By using highly defined experimental models to isolate these variables, a systematic analysis of in vivo influences on the selective induction of humoral and cell-mediated immunity will be performed.
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