The overall objective of this research proposal is to learn how MHC class-II restricted T cells (vis. Th) induce and regulate the immune response to influenza virus. We have approached this, during the previous granting period, by generating virus-specific Th clones from BALB/c mice through longterm culture and by sub- sequently testing the function of some of these Th clones in the promotion of anti-viral B cell responses in vivo after their adoptive transfer into athymic BALB/c recipient mice. We now propose to more fully explore this experimental system as follows: First, we plan to make a comprehensive determination of the factor profile (IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, LT, TNF) of all presently available Th clones by Northern blot analyses. Should the Th panel lack members of a defined Th subset, such as Th2, we then would make attempts to generate these additional Th clones. Examples of Th clones with clearly distinct factor profiles, such as Thi, Th2 and perhaps additional ones, will be tested for function in vivo after adoptive transfer into suitable recipient mice. This will include tests for promotion of i) B cell responses. ii) cytotoxic T cell responses. iii) memory B cell formation and iv) virus clearance. Selected Th clones will be studied also for survival in vivo and for migration and homing properties. We hope that this analysis will provide us with new insights into the functions of Th in the induction and regulation of an anti-viral immune response and of anti-viral defense mechanisms in vivo.
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