T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics
The proliferation and cytokine profiles of peripheral blood mononuclear cells (PBMC) from microfilaraemic (Mf+) subjects infected by Loa loa in response to antigens of several parasitic stages were compared with those from amicrofilaraemic (Mf−) individuals. While a strong lymphoproliferative response and consistent levels of both Th1 (IL‐2, interferon‐gamma (IFN‐γ)) and Th2 (IL‐4, IL‐5) type cytokines were observed in response to adult worm (AW) and microfilariae (Mf) antigen in Mf− individuals, Mf+ subjects were characterized by a T cell unresponsiveness, 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. Depletion of lymphocyte subpopulations indicated that T CD4+ were mainly involved in the specific cellular response. In contrast to other cytokines, IL‐10 was produced in response to all parasitic stages, in both Mf+ and Mf− patients. Neutralization of IL‐10 did not restore cytokine 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 unresponsiveness. Mf+ patients have lower Mf antigen‐specific IgG levels compared with Mf−, and there is a significant correlation between Mf antigen‐specific antibodies and IL‐5 responses. These findings suggest that Mf− status is correlated with T helper responsiveness, including proliferation and production of both Th1‐ and Th2‐type cytokines, whereas Mf+ status is characterized by unresponsiveness of the same cell population, induced and/or maintained by microfilariae.