Peripheral T cell tolerance may result from activation-induced cell death [1], anergy [1], and/or immune response modulation by regulatory T cells [2], In mice that express a transgenic receptor specific for peptide 111-119 of influenza hemagglutinin presented by Ed class II MHC molecules as well as hemagglutinin under central of the immunoglobulin-le promoter, we have found that anergic T cells [3] can also have immunoregulatory function and secrete IL-10 [4], In order to obtain information on molecular mechanisms involved in anergy and immunoregulation, we have compared expression levels of 1176 genes in anergic, naive, and recently activated CD4(+) T cells of the same specificity by gene array analysis. The results provide a plausible explanation for the anergic phenotype in terms of proliferation, provide new information on the surface phenotype of in vivo-generated anergic CD4(+) T cells, and yield clues with regard to new candidate genes that may be responsible for the restricted cytokine production of in vivo-anergized CD4+ T cells. The molecular fingerprints of such T cells should enable the tracking of this small population in the normal organism and the study of their role in immunoregulation.
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