The research project proposed herein examines the immune mechanisms resulting in an asymptomatic, hyporesponsive state among microfilaremic individuals (MF) with Iymphatic filariasis. It is hypothesized that MF subjects develop an Ag-specific tolerance in which antigen presenting cells (APC) generate co-stimulatory signals that promote a Th2.like pattern of cytokines which are: i) anti-inflammatory-,ii) produce counter regulatory cytokines (e.g.,IL.10, TGFbeta) that actively modulate Th1 responses, and iii) favor generation of immediate hypersensitivity responses (e.g. IgE and eosinophilia) that promote concomitant immunity. In addition, this proposal seeks to establish wbether the duration and intensity of exposure to infective larvae and worm burdens are the major factors which determine Th2 dominance among MF subjects.
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