Research
Derivation of CD4+ T-regs
In addition to dissecting CD8+ T cell-mediated immune regulation, we are also interested in the immune biology of CD4+CD25+FOXP3+ regulatory T cells (T-regs). These cells form an important arm of the immune system responsible for suppressing untoward immune responses. T-regs can be thymically derived or peripherally induced, even from CD4+CD25-FOXP3- T-cells. FOXP3 expression and in vitro suppressive activity are considered unique hallmarks of this dedicated and stable lineage of regulatory cells. However, our recent studies show that virtually all human CD4+CD25-FOXP3- T-cells and CD8+CD25-FOXP3- T-cells attain a transient FOXP3+CD25+ state during activation. In this state of activation, these cells possess the classic phenotype of T-regs, in that they express similar markers and inhibit in vitro proliferation of autologous CD4+CD25- T-cells. This state is characterized by suppressed IFN-g production and robust TNF-a and IL-10 production. Interestingly, the great majority of the activated cells eventually downregulate FOXP3 expression, with a concomitant drop in suppressive ability. Thus, in humans, FOXP3 expression and T-reg functionality are not exclusive features of a stable or unique lineage of T-cells, but may also be a transient state attained by almost all T-cells. These results warrant caution in interpreting human studies using FOXP3 and suppressive activity as readouts and suggest that attempts to induce “T-regs” may paradoxically result in induction of effector T-cells, unless stability is confirmed. Such induced T-regs and their role in various disease situations are a focus of several projects in the lab.
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Pillai, V., Ortega, S., Wang, C., and Karandiakr, N. (2007) Transient Regulatory T-Cells: A State Attained By All Activated Human T-Cells. Clin Immunol 123:1, 18–29.