Abstract
BackgroundTwo 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.MethodsTo 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).ResultsINF 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.ConclusionsOur 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.
Highlights
Th2 cells were initially characterized as expressing the cytokines – IL-4, IL-5 and IL-13 [1]
IL-5+Th2 cells have been found in greater frequencies (Fo) in patients with eosinophilic gastrointestinal disease, while peanut allergy was found to be associated with higher Fo of IL-52Th2 cells [5]
We show here data that filarial infection is associated with the expansion of two types of Th2 cells, one which produces IL-4 and IL-13 alone without IL-5 and the other which produces all three cytokines
Summary
Th2 cells were initially characterized as expressing the cytokines – IL-4, IL-5 and IL-13 [1]. Th2 cells can express a variety of other cytokines, these three cytokines remain the hallmark Th2 cytokines. While Th2 cells have generally been considered a homogenous population, recent reports provide evidence for subpopulations within the Th2 lineage [4]. Since the three established Th2 cytokines each play a non-redundant role in allergic disease pathology, it was postulated that these Th2 subsets might play an important role in allergic diseases. Two different Th2 subsets have been defined recently on the basis of IL-5 expression – an IL-5+Th2 subset and an IL-52Th2 subset in the setting of allergy. The role of these newly described CD4+ T cells subpopulations has not been explored in other contexts
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