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Keywords:

  • Mesenteric lymph node;
  • Parasitic helminth;
  • T cells

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.