The L3 of Brugia induces a Th2-polarized response following activation of an IL-4-producing CD4-CD8- αβ T cell population

Lymphatic filariasis in man is characterized by a profound bias in the immune response. Parasite-specific T(h)1 responses are dramatically down-regulated while T(h)2 responses dominate. We have used the infective larval stage of the nematode parasite Brugia pahangi, a potent T(h)2 inducer in naive mice, to examine cytokine production during the initiation phase of the response, For comparative purposes, the early cytokine transcription pattern elicited by microfilariae (mf), another life cycle stage of the parasite known to induce a primary T(h)1 response, was analysed in parallel. At 24 h post-infection (p.i.) a burst of IL-4 transcription was detected in the draining popliteal lymph node of L3-infected animals. IL-4 was the only cytokine transcript detectable at this early time point and was not present in mf-infected mice. From day 4 p.i. onwards, the L3 elicited a T(h)2 response as defined at the level of cytokine mRNA and protein production by CD4(+) cells. In contrast, mf stimulate high levels of IFN-gamma mRNA at day 4 p.i. in the absence of IL-4 or IL-10 induction. Cell selection analysis indicated that IL-4 produced at 24 h derived from a population of CD4(-)CD8(-) alpha beta T cells. These results suggest that triggering of an unusual double-negative T cell population to secrete IL-4 at the very outset of infection with the L3 of B. pahangi may be the critical factor favouring the development of antigen-specific T(h)2 cells in response to this stage of the parasite.