Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection

Abstract

Regulatory T cell responses to infectious organisms influence not only immunity and immunopathology, but also responses to bystander antigens. Mice infected with the gastrointestinal nematode parasite Heligmosomoides polygyrus show an early Th2‐dominated immune response (days 7–14), but by day 28 a strongly regulatory profile is evident with antigen‐specific IL‐10 release and elevated frequency of CD4⁺ T cells bearing surface TGF‐β. CD4⁺CD25⁺ T cells from infected mice show enhanced capacity to block in vitro effector T cell proliferation. CD4⁺CD25⁺ cell numbers expand dramatically during infection, with parallel growth of both CD25⁺Foxp3⁺ and CD25⁺Foxp3^– subsets. CTLA‐4 and glucocorticoid‐induced tolerance‐associated receptor, also associated with regulatory T cell function, become more prominent, due to both expanded CD25⁺ cell numbers and increased expression among the CD25^– population. Both intensity and frequency of CD103 expression by CD4⁺ T cells rise significantly, with greatest expansion among CD25⁺Foxp3⁺ cells. While TGF‐β expression is observed among both CD25⁺Foxp3⁺ and CD25⁺Foxp3^– subsets, it is the latter population which shows higher TGF‐β staining following infection. These data demonstrate in a chronic helminth infection that Foxp3⁺ regulatory T cells are stimulated, increasing CD103 expression in particular, but that significant changes occur to other populations including expansion of CD25⁺TGF‐β⁺Foxp3^– cells, and induction of CTLA‐4 on CD25^– non‐regulatory lymphocytes.