Polyclonal anergic CD4 T cells give rise to pathogenic TH1 and suppressive regulatory T cells during lymphopenia. (P1024)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.65-65.13
• Main Authors: Kalekar, Lokeshchandra, Jenkins, Marc, Mueller, Daniel
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.65.13

Anergy is defined as a state of hyporesponsiveness during which T cells fail to respond to their cognate antigen. Studying anergy using non-transgenic animals has been difficult due to lack of distinguishing markers for anergic cells. We identified CD73 and Folate Receptor 4 (FR4) to be highly expressed in anergic cells from transgenic animals following gene array analysis. Here, we show that CD44hi polyclonal CD4 T cells from non-transgenic animals expressing CD73 and FR4 are hyporesponsive following in vitro stimulation. Anergic T cells with specificity for a known self-antigen also express these markers. Adoptive transfer of these cells into lymphopenic animals leads to reversal of their anergic phenotype and differentiation to Tbet+ TH1 T cells and Foxp3+ regulatory T cells. Selective ablation of Treg cells, which arise following adoptive transfer, leads to accelerated weight-loss and lymphoproliferative disease in mice receiving these anergic cells. Our data suggest that anergy is not a stable state and anergic cells can reverse to diverse functional phenotypes. This finding has important implications for cancers, where anergy reversal and helper T cell differentiation in tumor infiltrating lymphocytes would be a favorable outcome, as well as for autoimmunity, where anergy reversal associated with Treg development could be beneficial.