KINETICS OF EX-VIVO CYTOKINE PRODUCTION BY SPLENOCYTES DURING MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME (MAIDS)

The role of T helper 1 (Th1) and T helper 2 (Th2) responses in the mur ine acquired immunodeficiency syndrome (MAIDS) is unclear, It has been suggested that differential activation of T cell subsets, particularl y a shift to Th2 cytokine production, may be associated with disease p rogression. To clarify the regulation of the cytokine network in the c ourse of MAIDS, we examined the kinetics of cytokine production by iso lated splenocytes. C57/BL6 mice were infected with the LP-BM5 mixture, The spleen cell proliferative response, together with IL-2, IFN-gamma , IL-10 and IL-4 production by unstimulated and ConA or anti-CDS MoAb- stimulated spleen cells, were determined at various times after inocul ation (weeks 1, 3, 6 and 9). Spleen cells isolated from murine leukemi a virus complex (LP-BM5) infected mice spontaneously produced signific ant amounts of IL-2 and IFN-gamma one and three weeks post-infection, compared to uninfected controls. The capacity of isolated T cells to p roduce the Th1 cytokines IL-2 and IFN-gamma in response to stimulation with ConA and anti-CD3 MoAb decreased after 3 weeks of infection, The fall in IL-2 production ran parallel to the fall in the T cell prolif erative response to ConA, IL-10 production in response to ConA and ant i-CD3 MoAb increased after three weeks post-inoculation, and followed the reverse kinetic pattern to IFN-gamma and IL-2, In contrast, no sig nificant spontaneous IL-4 production and no increase in IL-4 productio n in response to ConA or anti-CD3 MoAb occurred during the course of M AIDS, relative to uninfected controls. These results suggest that LP-B M5 infection leads to a fall in Th1 cytokine production rather than a clear switch to Th2 cytokine production.