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 (fo) 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 fo of both th2 subpopulations compared to the un and cp. interestingly,there was a positive correlation between the fo 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 fo 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.