T-HELPER RESPONSIVENESS IN HUMAN LOA LOA INFECTION - DEFECTIVE SPECIFIC PROLIFERATION AND CYTOKINE PRODUCTION BY CD4(-CELLS FROM MICROFILAREMIC SUBJECTS COMPARED WITH AMICROFILARAEMICS() T)

The proliferation and cytokine profiles of peripheral blood mononuclea r cells (PBMC) from microfilaraemic (Mf(+)) subjects infected by Loa l oa in response to antigens of several parasitic stages were compared w ith those from amicrofilaraemic (Mf(-)) individuals. While a strong ly mphoproliferative response and consistent levels of both Th1 (IL-2, in terferon-gamma (IFN-gamma)) and Th2 (IL-4, IL-5) type cytokines were o bserved in response to adult worm (AW) and microfilariae (Mf) antigen in Mf(-) individuals, Mf(+) subjects were characterized by a T cell un responsiveness, including proliferation, cytokine production and IL-2 mRNA expression. Conversely, T cell responsiveness to mitogens and non -specific antigen were similar in the two endemic populations. Depleti on of lymphocyte subpopulations indicated that T CD4(+) were mainly in volved in the specific cellular response. In contrast to other cytokin es, IL-10 was produced in response to all parasitic stages, in both Mf (+) and Mf(-) patients. Neutralization of IL-10 did not restore cytoki ne production in Mf(+) patients, while B7 mRNA expression was similar between Mf(+) and Mf(-) subjects in response to Mf antigen, suggesting that IL-10 was not the only factor responsible for T cell unresponsiv eness. Mf(+) patients have lower Mf antigen-specific IgG levels compar ed with Mf(-), and there is a significant correlation between Mf antig en-specific antibodies and IL-5 responses. These findings suggest that Mf(-) status is correlated with T helper responsiveness, including pr oliferation and production of both Th1- and Th2-type cytokines, wherea s Mf(+) status is characterized by unresponsiveness of the same cell p opulation, induced and/or maintained by microfilariae.