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Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford, United Kingdom
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
E
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.
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