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.

Abstract

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.

• Authors: Rajamanickam Anuradha, Parakkal Jovvian George, Luke E Hanna, Vedachalam Chandrasekaran, P Paul Kumaran, Thomas B Nutman, Subash Babu
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 8 Issue 1 Pg. e2658 ( 2014) ISSN: 1935-2735 [Electronic] United States
• PMID: 24498448 (Publication Type: Journal Article)

Chemical References

• Antigens, Helminth
• IL10 protein, human
• IL5 protein, human
• Interleukin-5
• Transforming Growth Factor beta
• Interleukin-10

Topics

• Adult
• Aged
• Animals
• Antigens, Helminth (immunology)
• Elephantiasis, Filarial (immunology)
• Female
• Humans
• Interleukin-10 (metabolism)
• Interleukin-5 (analysis)
• Male
• Middle Aged
• T-Lymphocyte Subsets (chemistry, immunology)
• Th2 Cells (chemistry, immunology)
• Transforming Growth Factor beta (metabolism)
• Young Adult