We propose to study the regulation of lymphokine secretion in subsets of helper T cells. We have substantial evidence that two subsets of helper T cells exist and that those T cells are able to secrete IL4 and IL5 (Th2) develop only after priming. (1) We will characterize and compare the subpopulations of normal helper T cells which secrete the lymphokines IL2 and IFN gamma (Th1) versus those which secrete IL4 and IL4 (Th2). We will study the kinetics of their appearance and the requirements for their induction including the lymphokines which regulate their development. We will also delineate the phenotype of their precursors. (2) We will determine the frequency of the two types of helpers among populations of lymphoid cells derived from different lymphoid organs both before and after priming using biological assays and by detecting cell synthesizing lymphokines by fluorescent staining. (3) We will use both immunological techniques and molecular assays to investigate the in situ production of lymphokines by T cells in normal mice undergoing an immune response. We will study the kinetics of development and the distribution of lymphokine- secreting T cells during an immune response. Characterization of T cells secreting distinct lymphokines which have different effects on the multiple cells involved in immune response will provide valuable information about the regulation of the immune response which is necessary for the development of effective immunotherapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026887-05
Application #
3140902
Study Section
Experimental Immunology Study Section (EI)
Project Start
1988-07-01
Project End
1994-03-31
Budget Start
1992-07-01
Budget End
1994-03-31
Support Year
5
Fiscal Year
1992
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
Jelley-Gibbs, Dawn M; Brown, Deborah M; Dibble, John P et al. (2005) Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J Exp Med 202:697-706
Misra, Ravi S; Jelley-Gibbs, Dawn M; Russell, Jennifer Q et al. (2005) Effector CD4+ T cells generate intermediate caspase activity and cleavage of caspase-8 substrates. J Immunol 174:3999-4009
Jelley-Gibbs, Dawn M; Dibble, John P; Filipson, Svetlana et al. (2005) Repeated stimulation of CD4 effector T cells can limit their protective function. J Exp Med 201:1101-12
Li, JiChu; Huston, Gail; Swain, Susan L (2003) IL-7 promotes the transition of CD4 effectors to persistent memory cells. J Exp Med 198:1807-15
Yen, Michael H; Lepak, Nancy; Swain, Susan L (2002) Induction of CD4 T cell changes in murine AIDS is dependent on costimulation and involves a dysregulation of homeostasis. J Immunol 169:722-31
Cauley, L S; Miller, E E; Yen, M et al. (2000) Superantigen-induced CD4 T cell tolerance mediated by myeloid cells and IFN-gamma. J Immunol 165:6056-66
Rogers, P R; Dubey, C; Swain, S L (2000) Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen. J Immunol 164:2338-46
Jelley-Gibbs, D M; Lepak, N M; Yen, M et al. (2000) Two distinct stages in the transition from naive CD4 T cells to effectors, early antigen-dependent and late cytokine-driven expansion and differentiation. J Immunol 165:5017-26
Swain, S L (2000) CD4 T-cell memory can persist in the absence of class II. Philos Trans R Soc Lond B Biol Sci 355:407-11
Carter, L L; Swain, S L (1998) From naive to memory. Development and regulation of CD4+ T cell responses. Immunol Res 18:1-13

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