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.
National Institutes of Health-International Center for Excellence in Research, Chennai, India.
Rajamanickam
R
Anuradha
National Institutes of Health-International Center for Excellence in Research, Chennai, India.
Parakkal Jovvian
PJ
George
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Luke E
LE
Hanna
National Institute for Research in Tuberculosis, Chennai, India.
Vedachalam
V
Chandrasekaran
National Institute for Research in Tuberculosis, Chennai, India.
P Paul
PP
Kumaran
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Thomas B
TB
Nutman
National Institutes of Health-International Center for Excellence in Research, Chennai, India ; Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Subash
S
Babu
D000328:Adult; D000368:Aged; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D004605:Elephantiasis, Filarial / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015848:Interleukin-5 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D018418:Th2 Cells / Q000737:chemistry / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055815:Young Adult
D000947:Antigens, Helminth; C508609:IL10 protein, human; C508599:IL5 protein, human; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D016753:Interleukin-10