| Research Abstract |
This study demonstrates that CD4+ T cells specific for an altered self-antigen differentiate to T cells secreting transforming growth factor (TGF)-β1.In this study, we utilized mice expressing an altered peptide ligand (APL) containing a single-amino acid substitution of moth cytochrome c 88-103 peptide (MCC). In these mice, antigen specific T cells escaping thymic negative selection ifferentiated into T cells with an effector/memory phenotype, CD44^<high>, CD45RB^<low>, CD62L^- and CD25^<intermediate>. The expression of CD25 and high levels of CD44 was initiated in the thymus during the development from CD4^+CD8^+ to CD4^+ ; a large proportion of maturing CD4^+ thymocytes expressed both CD25 and high levels of CD44.Upon antigen stimulation, CD4^+ T cells derived from these mice did not proliferate or secrete IL-2 but secreted TGF-β1.Neutralizing antibodies to TGF-pβ1 reversed the impaired proliferative responses to the antigen, suggesting that TGF-β1 secreted from these T cells negatively regulates T cell responses.
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