Roles for both CD4+ and CD8+ T cells in protective immunity against Onchocerca lienalis microfilariae in the mouse

Abstract

Mice inoculated with microfilariae of the filarial nematode Onchocerca lienalis clear their parasites from the skin over a period of 3 to 4 months and are highly resistant to a challenge infection. The adoptive transfer of spleen cells at various time points following primary and secondary infections of mice shows that exposures of 50 days or greater are required for the generation of lymphocytes capable of transferring protection to naive recipients. This adoptive transfer of protection with spleen cells from infection-primed mice partitions with the T lymphocyte population. In contrast, the passive transfer of protection with spleen-derived B cells, or sera taken at various time points following infection was not achieved. Moreover, there was no detectable synergistic effect when B and T cells were co-administered to recipient animals. Depletion of CD4+ and CD8+ T cells with monoclonal antibodies shows that CD8+ T cells have some regulatory effect on parasite establishment early in primary infection, but this is later superseded by CD4+ T cell reactivity that is predominant both when primary infection microfilariae are cleared and also during resistance to reinfection. Measurement of cytokines in the sera of mice undergoing primary and secondary infections support a microfilariae-induced Th2 activity, with high levels of IL-5 that are sustained upon reinfection, and low levels of IFN-gamma that are negligible at the time when mice are most strongly immune.