Plasmodium yoelii: Cellular Immune-Responses in Splenectomized and Normal Mice

Abstract

Spleen and lymph node cells from Plasmodium yoelii 17X-infected, C57BL/6 (B6), and DBA/2 (D2) mice were cultured in vitro with parasite antigens. The ability of these cells to proliferate was quantified by uptake of [ 3H]thymidine and ELISA was used to measure secretion of IFN-γ and IL-5. B6 mice are relatively susceptible to P. yoelii 17X infection compared to D2 mice. Susceptible mouse strains develop higher levels of parasitemia, become more anemic, and take longer to resolve their infections than do resistant strains. Following splenectomy, D2 mice resisted P. yoelii 17X infections as well as did sham-operated controls, but splenectomized B6 mice failed to resolve their infections and all died. Spleen cells from infected mice of either strain were activated in vitro as evidenced by their proliferation in the absence of exogenous antigen. When malaria antigen was added to these cultures, cells from resistant D2 mice responded strongly with increased proliferation, whereas cells from susceptible B6 mice responded weakly, and on Day 14 postinfection, responses were actually suppressed. Mesenteric lymph node cells from infected B6 and D2 mice did not proliferate in the presence or absence of P. yoelii 17X antigen unless the spleen was removed. Following splenectomy, mesenteric lymph node cells from D2 mice, but not B6 mice, proliferated strongly compared to cells from sham-operated controls. IFN-γ and IL-5 production from spleen and lymph node cells was measured following in vitro stimulation with P. yoelii 17X antigen. Spleen cells from D2 mice produced levels of IFN-γ increased over those of cells from B6 mice. Following splenectomy, mesenteric and peripheral lymph node cells from D2 mice showed increased IFN-γ production not evident when the spleen was present. Lymph node cells from splenectomized B6 mice also showed increased IFN-γ production, but the levels were significantly lower than those of splenectomized D2 mice. No significant production of IL-5 was measured in the supernatants of cultured cells from either strain, whether splenectomized or not. These data suggest that increased susceptibility to infection may be associated with depressed proliferative and IFN-γ responses to malaria antigen, and that lymph node cells, particularly in resistant D2 mice, respond in a compensatory manner when the spleen is removed.