The long-term objective of this project is to investigate the role of helper T cells and their products in the B cell response. Recently, it has become clear that different subsets of helper T cells produce distinct patterns of lymphokines, and that subsets of T cells can also be defined based on their stage of development.
The specific aims of this project are to determine the effects of isolated subsets of helper cells on the response of distinct B cell subpopulations and to determine the mechanism by which helper T cells direct B cells to synthesize distinct isotypes of antibody. The experiments are also designed to evaluate the relative contributions of direct interaction with T cells, of lymphokines and of antigen in the response of B cells. The results will help us to understand the difference seen between responses to pathogens and antigen never before encountered by the organism and memory immune responses. These findings will also help us understand how distinct types of immune responses, represented by the production of antibodies of different isotypes, develop and could suggest ways of influencing their development. Such data will also contribute to basic knowledge about the possible effects of lymphokines versus helper T cells which will be important for evaluating the likely efficacy of therapeutic approaches involving lymphokines versus introduction of cells. Finally, a better understanding of the roles played by helper T cells in different functional B cell responses should help provide the basic foundation to help us understand how dysfunction of helpers could contribute to immunodeficiency, autoimmunity and cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022125-09
Application #
3132855
Study Section
Experimental Immunology Study Section (EI)
Project Start
1985-09-30
Project End
1995-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Kamperschroer, Cris; Dibble, John P; Meents, Dana L et al. (2006) SAP is required for Th cell function and for immunity to influenza. J Immunol 177:5317-27
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Croft, M; Swain, S L (1995) Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines. J Immunol 154:4269-82
Dubey, C; Croft, M; Swain, S L (1995) Costimulatory requirements of naive CD4+ T cells. ICAM-1 or B7-1 can costimulate naive CD4 T cell activation but both are required for optimum response. J Immunol 155:45-57

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