Type 1 CD8+ T cell responses during infection with the helminth Schistosoma mansoni.
IL-4 promotes the development of type 2 CD8+ T cells. In mice infected with the helminth Schistosoma mansoni, the Th response is overtly Th2-like, creating an environment rich in IL-4. Consequently, we examined whether CD8+ subset development in schistosome-infected mice is biased in a type 2 direction; this is of interest because CD8+ cells have been proposed to play an immunoregulatory role during schistosomiasis. Contrary to expectation, our data indicate that the CD8+ cell response in infected mice is strongly type 1-like. Thus, infection with S. mansoni leads to the development of concurrent Th2 and type 1 CD8+ cell responses. Cytokine production by type 1 CD8+ cells is dependent upon help from CD4+ cells; this helper activity can be substituted by exogenous IL-2 or IL-4. Since Th cells from infected mice make little IL-2 but large amounts of IL-4, we propose that IL-4 is likely to be the physiologic mediator of help in infected animals, a view supported by the ability of mAbs against IL-4R and IL-4 to reduce IFN-gamma production by splenocytes in vitro. CD8+ cells from infected mice are able to produce IFN-gamma in response to schistosome Ag presented by bone marrow-derived APC. A regulatory role for the CD8+ cells is implied by the observation that CD8+ cell-depleted splenocytes from infected mice exhibit increased proliferative responses and IL-4 production in response to mAb anti-CD3. These findings suggest that in mice infected with schistosomes there exists a regulatory pathway in which type 1 CD8+ cells, under the control of IL-4, dampen immunopathologic type 2 responses.
Pedras-Vasconcelos
J A
JA
Department of Microbiology and Immunology, Conell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Pearce
E J
EJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma