Schistosome infection stimulates host CD4(+) T helper cell and B-cell responses against a novel egg antigen, thioredoxin peroxidase

Egg granuloma formation during schistosome infections is mediated by CD4(+) T helper (Th) cells sensitized to egg antigens; however, most of the relev ant sensitizing egg antigens are still unknown, Here we show that schistoso me thioredoxin peroxidase (TPx)-1 is a novel T- and B-cell egg antigen in s chistosome-infected mice. CD4(+) Th cell responses to fractionated egg comp onents identified a significant response against a 26-kDa antigen; a partia l amino acid sequence of this antigen was found to be identical to that of Schistosoma mansoni TPx-1, The native TPx-1 elicited significant proliferat ive responses as well as gamma interferon (IFN-gamma), interleukin-2 (IL-2) , IL-4, and IL-5 secretion in CD4(+) cells from 8.5-week-infected CBA and C 57BL/6 mice. By comparison, recombinant TPx-1 elicited a smaller, more type I-polarized response, with significant production of IFN-gamma and IL-2, l ess IL-5, and essentially no IL-4. In C57BL/6 mice the responses to TPx-1 w ere relatively more prominent than that directed against the major egg anti gen, Sm-p40, whereas in CBA mice the reverse was true. B-cell responses wer e also monitored in infected C57BL/6, C3H, CBA, and BALB/c mice. All strain s had significant antibody levels against the TPx-1 protein, but the most s ignificant antibody production ensued following parasite oviposition, TPx-1 was localized in eggs and shown to be secreted by eggs, The identification of egg antigens is important to understand the specific basis of granuloma formation in schistosome infections and may prove to be useful in strategi es to ameliorate pathological responses.