Cellular immune responses in mice infected with the intestinal nematode Trichuris muris

CBA and B10.BR mice show variation in immune response to the intestinal nem atode Trichuris muris. CBA mice develop strong resistance, eliminating worm s from the intestine; B10BR mice are permissive and develop chronic infecti ons. It is already known that resistance and permissiveness reflect differe ntial T helper responses. The data reported here show that resistant CBA mi ce express good antigen-specific lymphocyte proliferative responses to infe ction, whereas cells from B10.BR mice are relatively anergic, although stil l responsive to Concanavalin A (ConA). The possibility that the altered pro liferative responsiveness seen in infected B10.BR mice reflected quantitati ve or qualitative changes in T helper cells was examined by comparing cytok ine production and expression of cell surface markers (CD4, CD8, and CD28) in mesenteric lymph node cells and spleen cells from both strains and compa ring these with the characteristics of cells from resistant CBA mice and fr om CBA mice that had been rendered permissive to infection by a combination of irradiation and corticosteroid treatment. As expected, cells from B10.B R mice produced high levels of interferon-gamma (IFN-gamma), whereas those from CBA mice released high levels of IL-5, whether stimulated with adult w orm somatic antigens, excretory/secretory antigens, or ConA. Immunosuppress ed CBA mice produced high levels of both IFN-gamma and IL-5 throughout the experiment. FAGS analysis revealed a decrease of CD4(+) and an initial incr ease in CD8(+) cells in all infected mice. No major changes occurred in the relative proportion of CD28(+) cells. Further evaluation of the CD28 costi mulatory molecule, measured as mean fluorescence intensity, displayed down- regulation in permissive and immunosuppressed mice. The data obtained sugge st that lymphocyte unresponsiveness and permissiveness to T. muris infectio n may be associated with a down-regulation or an initially reduced expressi on of costimulatory CD28 molecules. (C) 1999 Academic Press.