Cytokine production from murine CD4 and CD8 cells after mannan-MUC1 immunization

Immunotherapy with oxidized mannan-MUC1 fusion protein (M-FP) leads to a T1 immune response characterized by the generation of cytotoxic T lymphocytes (CTL), few antibodies, secretion of interleukin-2 (IL-2), IL-12, and inter feron-gamma and tumor protection. Immunotherapy with reduced M-FP or fusion protein (FP) alone leads to a T2 immune response characterized by the gene ration of MUC1 antibodies, few CTL, IL-4 secretion, and no tumor protection . In these studies, cytokine production from T cells was measured from cult ures containing whole spleens. We now report the cytokine secretion pattern s from spleen cells separated into CD4(+) and CD8(+) T cells obtained from mice immunized with either oxidized M-FP, reduced M-FP or FP, or the simult aneous administration of oxidized M-FP and FP, Immunization with oxidized M -FP led to the secretion of T1 cytokines from CD8(+) T cells (IL-2, IFN-gam ma, and tumor necrosis factor-alpha [TNF-alpha]) and from CD4(+) T cells (I L-2 and IFN-gamma), IL-12 production, presumably from activated macrophages , was observed in CD8(+) but not CD4(+) cultures, Immunization with either reduced M-FP or FP led to the secretion of predominantly T2 cytokines from CD4(+) T cells (IL-4 and IL-10) and IL-2 production in both CD4(+) and CD8 T cell cultures. The simultaneous immunization of both oxidized M-FP and F P led to the production of both T1 and T2 cytokines from CD8(+) T cells (IL -2, IFN-gamma, and TNF-alpha) and CD4(+) cells (IL-2, IFN-gamma, IL-4, and IL-10) and IL-12 production in CD8(+) cultures that is, both types of immun e responses could occur together. The results demonstrate that the cellular immune response observed in oxidized M-FP-immunized mice is indeed depende nt on the T1 cytokine profile secreted by CD8(+) T cells, and the simultane ous production of both T1 and T2 cytokines is not cross-inhibitory.