Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4+ T cell responses
AUTOR(ES)
Chambers, Cynthia A.
FONTE
The National Academy of Sciences
RESUMO
CTLA-4-deficient mice develop a fatal lymphoproliferative disorder, characterized by polyclonal expansion of peripheral lymphocytes. To examine the effect of restricting the CD4+ TCR repertoire on the phenotype of CTLA-4-deficient mice and to assess the influence of CTLA-4 on peptide-specific CD4+ T cell responses in vitro, an MHC class II-restricted T cell receptor (AND TCR) transgene was introduced into the CTLA-4−/− animals. The expression of the AND TCR transgene by CD4+ T cells delays but does not prevent the lymphoproliferation in the CTLA-4−/− mice. The CD4+ T cells become preferentially activated and expand. Interestingly, young AND TCR+ CTLA-4−/− mice carrying a null mutation in the rag-1 gene remain healthy and the T cells maintain a naive phenotype until later in life. We demonstrate that CTLA-4 regulates the peptide-specific proliferative response generated by naive and previously activated AND TCR+ RAG−/− T cells in vitro. The absence of CTLA-4 also augments the responder frequency of cytokine-secreting AND TCR+ RAG−/− T cells. These results demonstrate that CTLA-4 is a key regulator of peptide-specific CD4+ T cell responses and support the model that CTLA-4 plays a differential role in maintaining T cell homeostasis of CD4+ vs. CD8+ T cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17563Documentos Relacionados
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