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Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the size, reactivity, and function of a primed pool of [CD4.sup.+] T cells
- Source :
- Proceedings of the National Academy of Sciences of the United States. Nov 7, 2000, Vol. 97 Issue 23, 12711
- Publication Year :
- 2000
-
Abstract
- We examined how cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates heterogeneous [CD4.sup.+] T cell responses by using experimental autoimmune encephalomyelitis (EAE), a [CD4.sup.+] T cell-mediated disease that is subject to regulation by CTLA-4. Disease incidence and severity were used as measures of in vivo [CD4.sup.+] T cell responses. The frequency, cytokine production, and reactivity of primed T cells were determined from animals immunized with proteolipid protein (PLP)-139-151 (disease agonist), PLP-Q (disease antagonist), or both peptides, and treated with control or anti-CTLA-4 antibody to analyze the responding population. CTLA-4 blockade exacerbated disease in PLP-139-151-primed animals and overcame disease antagonism in coimmunized animals, but did not permit disease induction in PLP-Q-primed animals. Experimental autoimmune encephalomyelitis enhancement was associated with increased frequencies of cytokine-producing cells and increased ratios of IFN-[Gamma] to IL-4 secretors responsive to PLP-139-151. Priming with PLP-Q elicited IL-4 and IL-2, but not IFN-[Gamma] secretors cross-reactive with PLP-139-151. Strikingly, CTLA-4 blockade was found to decrease rather than increase the frequencies of cross-reactive IL-4 and IL-2 secretors. Thus, CTLA-4 engagement limits the size, but increases the breadth, of reactivity of a primed pool of [CD4.sup.+] T cells, consequently regulating its function.
Details
- ISSN :
- 00278424
- Volume :
- 97
- Issue :
- 23
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.67408714