T. cruzi-induced Protective and Pathologic CD4 Responses

Infectious Disease Research Institute, Seattle WA

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Abstract

DESCRIPTION (provided by applicant): The long-term objectives of this research are to understand the mechanisms of chronic inflammatory diseases. Infections initiate or perpetuate many chronic inflammatory diseases. Trypanosoma cruzi infection of mice is an excellent system to investigate infection-induced chronic inflammation. During T. cruzi infection of mammals the CD4 T cell response is critical in controlling the parasite and in generating the chronic inflammation. The T. cruzi antigens of the CD4 response have been unknown limiting further investigations. The T. cruzi trans-sialidase superfamily simultaneously expresses a large number of variant epitopes. The effect of these variant epitopes on the T cell response is unknown. During T. cruzi infection an epitope, epitope 1, of the trans-sialidase superfamily protein SA85-.1, appears to stimulate a large CD4 response. This project investigates this response's contribution in controlling the parasite and causing the ensuing chronic inflammation. Cellular immunology and molecular biology techniques will be used to develop epitope 1- specific T cell clones and TCR transgenic mice. During T. cruzi infection, these T cells will be used to analyze: the size and specificity of the SA85-1.1 protein and epitope 1 responses; the mechanisms used by epitope 1 specific T cell clones to protect, and the clones' ability to cause chronic inflammation; and the naive epitope 1 specific CD4 T cell response and these cells' ability to control T. cruzi and cause chronic inflammation. Completion of these aims will clarify the relationship of T. cruzi-induced protective and inflammatory T cell responses, and will provide insight into infection-induced T cell responses and chronic inflammatory diseases.