Parasite-Antigen Driven Expansion of IL-5(−) and IL-5(+) Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ

BACKGROUND: Two different Th2 subsets have been defined recently on the basis of IL-5 expression – an IL-5(+)Th2 subset and an IL-5(−)Th2 subset in the setting of allergy. However, the role of these newly described CD4(+) T cells subpopulations has not been explored in other contexts. METHODS: To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5(+)IL-4(+)IL-13(+) CD4(+) T cells and IL-5(−)IL-4 IL-13(+) CD4(+) T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (F(o)) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP). RESULTS: INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced F(o) of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the F(o) of IL-5(+)Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4(+)IL-5(−)Th2 subpopulation and the levels of parasite antigen – specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGFβ demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased F(o) of both Th2 subsets. CONCLUSIONS: Our findings suggest that both IL-5(+) and IL-5(−)Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes.