Antigenic specificities of intestinal CD4+Foxp3+ T cells.

In the intestine, regulatory T cells that express Foxp3 transcription factor (Tregs) are critical for
the regulation of adaptive immune response to commensal antigens. Tregs differentiate in the
thymus (tTregs) or convert from naive, peripheral Foxp3- T cells (pTregs).It is currently unclear
if tTregs and pTregs have redundant or complimentary role in maintenance of intestinal
homeostasis. Our long term goal is to understand how the homeostatic balance in the intestine
depends on pTregs and tTregs, and how their TCR repertoires can change by exposure to
antibiotics. Our central hypothesis is that clonal expansions and selective trophism of tTregs are
essential to sustain intestinal equilibrium. To test our hypothesis we propose two specific aims.
First we will characterize TCRs on mucosal Tregs in the intestine of CNS1mut mice that lack
pTregs but have normal tTregs. In addition, in these mice CD4+ T cells express semi diverse
repertoire of TCRs and activated Tregs express green fluorescent protein (GFP). We
hypothesize that in these mice mucosal tTregs will control intestinal naïve and effector T cells,
and that TCRs expressed by tTregs can be specific to commensal antigens. Second, we will
investigate how antibiotic treatment early in life can permanently change microbial flora and
clonal diversity of intestinal Tregs. We hypothesize that changes in the diversity for microbial
flora induced by neonatal exposure to antibiotics permanently alter repertoire of intestinal tTregs.