CD4+ TH1 and TH2 cells differ in several ways. They secrete different cytokines. The express different cell surface molecules and different transcription factors. These different molecules expressed by TH1 and TH2 contribute to their unique functions and to mechanisms that specifically regulate the growth and differentiation of the subsets. We have recently identified a new functional difference between TH1 and TH2 cells. As part of a series of studies to understand better how CD8+ T cells regulate CD4+ T cell responses, we identified a CD8+ T cell response that was Qa-1-restricted and VBeta8-specific and we cloned CD8+ T cell hybridomas with the specificity. These hybridomas respond to TH1 cells and to a lymphoma that express VBeta8 TCR and Qa-1a but not to VBeta8+ Qa-1b+ cells. The hybridomas, however, do not respond to Qa-1a+ VBeta8+ TH2 cells. This is true even for paris of TH1 and TH2 cells that express identical TCRBeta chains. This difference is not due to an affect of cytokines or other products secreted by the CD4+ cells during the time period examined. The data instead suggest that TH1 and TH2 cells differ either in antigen processing or in the expression of cell surface molecules important in T-T interactions. Consistent with this, the difference between TH1 and TH2 cells is preserved after fixation of the CD4+ cells. In this proposal, we will determine the molecular difference(s) between TH1 and TH2 cells that account(s) for their differential ability to be recognized by antigen-specific CD8+ T cells. We will determine when during TH subset differentiation this difference emerges. We will determine if this difference uniquely applies to the recognition of TCR peptide presented by Qa-1 or if CD8+ T cells specific for other peptides presented by MHC class I molecules also distinguish between TH1 and TH2 targets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI044927-03
Application #
6362395
Study Section
Immunobiology Study Section (IMB)
Program Officer
Kehn, Patricia J
Project Start
1999-03-01
Project End
2004-02-29
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
3
Fiscal Year
2001
Total Cost
$248,857
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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Goldstein, Itamar; Ben-Horin, Shomron; Li, Jianfeng et al. (2003) Expression of the alpha1beta1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells. J Clin Invest 112:1444-54
Yan, Shirley ShiDu; Wu, Zhi-Ying; Zhang, Hui Ping et al. (2003) Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nat Med 9:287-93
Jiang, H; Braunstein, N S; Yu, B et al. (2001) CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice. Proc Natl Acad Sci U S A 98:6301-6