Abstract

The focus of this proposal is to study the influence of functionally distinct subsets of CD4 T lymphocytes on B cell and macrophage activation and function. Previous studies in this laboratory have shown that CD4 T cells can be subdivided into two functionally distinct subsets whose functional capabilities correlate with the unique panel of cytokines each releases upon activation. Given that their functions appear quite distinct with one subset playing a primary role in B cell activation, IgE secretion, mast cell and eosinophil amplification and the other subset mediating delayed type hypersensitivity responses, cytolysis and macrophage activation, it would appear that each subset would contribute to immunity against microorganisms which are either extracellular or intracellular microorganisms, respectively. The present studies will address the following issues. 1) What is the function of cloned and uncloned subsets of CD4 in B cell and macrophage activation in vivo and in vitro; 2) What is the lineage relationship between the two subsets of T cells in terms of their effector function and phenotype if individual subsets are used to reconstitute B or scid mice; and 3) Are experimental models exhibiting deficiency in a particular type of immunity examples of deficiencies in the effector functions provided by a subset of CD4 T cell.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038350-12
Application #
3176438
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-03-01
Project End
1994-02-28
Budget Start
1992-03-01
Budget End
1993-02-28
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Chen, Jonathan H; Perry, Curtis J; Tsui, Yao-Chen et al. (2015) Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection. Nat Med 21:327-34
Whitmire, Jason K; Asano, Mary S; Kaech, Susan M et al. (2009) Requirement of B cells for generating CD4+ T cell memory. J Immunol 182:1868-76
Jackman, Rachael P; Balamuth, Fran; Bottomly, Kim (2007) CTLA-4 differentially regulates the immunological synapse in CD4 T cell subsets. J Immunol 178:5543-51
Meyer zum Bueschenfelde, Christian O; Unternaehrer, Julia; Mellman, Ira et al. (2004) Regulated recruitment of MHC class II and costimulatory molecules to lipid rafts in dendritic cells. J Immunol 173:6119-24
Czyzyk, Jan; Brogdon, Jennifer L; Badou, Abdallah et al. (2003) Activation of CD4 T cells by Raf-independent effectors of Ras. Proc Natl Acad Sci U S A 100:6003-8
Boursalian, T E; Bottomly, K (1999) Stability of naive and memory phenotypes on resting CD4 T cells in vivo. J Immunol 162:9-16
Boursalian, T E; Bottomly, K (1999) Survival of naive CD4 T cells: roles of restricting versus selecting MHC class II and cytokine milieu. J Immunol 162:3795-801
Metz, D P; Farber, D L; Taylor, T et al. (1998) Differential role of CTLA-4 in regulation of resting memory versus naive CD4 T cell activation. J Immunol 161:5855-61
Farber, D L; Acuto, O; Bottomly, K (1997) Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. Eur J Immunol 27:2094-101
Metz, D P; Farber, D L; Konig, R et al. (1997) Regulation of memory CD4 T cell adhesion by CD4-MHC class II interaction. J Immunol 159:2567-73

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