Larkin Joseph, Picca Cristina Cozzo, Caton Andrew J
The Wistar Institute, Philadelphia, PA 19104, USA.
Eur J Immunol. 2007 Jan;37(1):139-46. doi: 10.1002/eji.200636577.
CD4+ CD25+ Foxp3+ regulatory T (Treg) cells can undergo both thymic selection and peripheral expansion in response to self peptides that are agonists for their T cell receptors (TCR). However, the specificity by which these TCR must recognize peptide:MHC complexes to activate Treg cell function is not known. We show that CD4+ CD25+ Foxp3+ Treg cells can mediate suppression in response to peptides that are only weakly cross-reactive with the self peptide that induced their formation in vivo. Moreover, suppression could be efficiently activated by peptide analogs that were inefficient at inducing CD69 up-regulation, and that also induced little or no proliferation of naïve CD4+ CD25- Foxp3- T cells expressing the same TCR. These findings provide evidence that self peptide-specific CD4+ CD25+ Foxp3+ Treg cells can exert regulatory function in response to self- and/or pathogen-derived peptides with which they are only weakly cross-reactive.
CD4+ CD25+ Foxp3+调节性T（Treg）细胞可经历胸腺选择和外周扩增，以响应作为其T细胞受体（TCR）激动剂的自身肽。然而，这些TCR识别肽：MHC复合物以激活Treg细胞功能的特异性尚不清楚。我们发现，CD4+ CD25+ Foxp3+ Treg细胞可对仅与在体内诱导其形成的自身肽弱交叉反应的肽作出反应，介导抑制作用。此外，肽类似物可有效激活抑制作用，这些肽类似物在诱导CD69上调方面效率低下，并且对表达相同TCR的初始CD4+ CD25- Foxp3- T细胞几乎不诱导增殖或不诱导增殖。这些发现提供了证据，表明自身肽特异性CD4+ CD25+ Foxp3+ Treg细胞可对与其仅弱交叉反应的自身和/或病原体衍生肽作出反应，发挥调节功能。
