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There is now compelling evidence for subpopulations of CD4+ T cells whose role is to prevent immune pathology in both autoimmunity and transplantation. We have cloned CD4+ T cells against a male transplantation Ag that, unlike Th1 or Th2 clones, suppresses the rejection of male skin grafts and are therefore considered examples of regulatory T cells. We have identified, using serial analysis of gene expression, transcripts that are overexpressed in regulatory T cells compared with Th1 and Th2 clones. Some of these transcripts are increased in tolerated rather than rejecting skin grafts and in addition are expressed by the natural regulatory CD4+CD25+ subpopulation of naive mice. These genes include prepro-enkephalin, GM2 ganglioside activator protein, glucocorticoid-induced TNFR superfamily member 18, and integrin alpha(E)beta(7). They seem to represent a subset of transcripts shared with Th2 cells, suggesting that transplantation tolerance and normal immunoregulation may represent a unique form of Th2-like differentiation.


Journal article


J Immunol

Publication Date





1069 - 1079


Adoptive Transfer, Amino Acid Sequence, Animals, CD4-Positive T-Lymphocytes, Clone Cells, Epitopes, T-Lymphocyte, Female, Fluorescent Antibody Technique, Direct, Gene Expression Profiling, Gene Expression Regulation, Gene Library, Graft Rejection, Male, Mice, Mice, Inbred CBA, Mice, Transgenic, Molecular Sequence Data, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction, Spleen, T-Lymphocyte Subsets, Th1 Cells, Th2 Cells, Transcription, Genetic, Transplantation Tolerance