CONTROL OF PARASITEMIA AND SURVIVAL DURING TRYPANOSOMA-BRUCEI-BRUCEI INFECTION IS RELATED TO STRAIN-DEPENDENT ABILITY TO PRODUCE IL-4

We studied non-MHC gene-dependent expression of a number of cytokines in relation to host defense and survival during Trypanosoma brucei bro cei (Tbb) infection in mice, In particular, the role of IL-4 was explo red with use of genomically L-4-disrupted mice and in vivo Ab blocking , Splenocytes from MHC-identical B10.Q (relatively resistant) mice sho wed day 5 postinfection higher numbers of IL-4 mRNA expressing cells t han C3H.Q (highly susceptible), A trypanosome-derived lymphocyte trigg ering factor, which is released by Tbb to polyclonally activate CD8(+) T cells, stimulated naive splenocytes in vitro to a higher IL-4 respo nse in B10.Q than in C3H.Q mice, The C3H.Q mice developed an extremely high parasitemia, showed a low Ab response against the variant surfac e glycoprotein (VSG), and had a mean survival time of 42 days, Convers ely, B10.Q mice had lower parasitemia, mounted higher anti-VSG respons e, and had a mean survival time of 56 days, Deletion of the IL-4 gene had no influence on the infection in C3H.Q mice, while in B10.Q mice t he deletion was associated with lower anti-VSG Ab levels and higher pa rasitemia, Paradoxically, B10.Q mice with disrupted IL-4 gene survived longer than the wild type, Anti-IL-4 Ab-blocking experiments in vivo displayed an enhanced parasitemia and prolonged survival in infected B 10.Q mice, We conclude that 1) a non-MHC gene-related and CD8(+)-depen dent ability to produce IL-4 partly determines the susceptibility to T bb infection; and 2) IL-4, although involved in controlling the levels of parasitemia by its effects on immunoglobulin synthesis, also can h ave toxic effects on the animals.