Parasite antigen-specific, IL-4-, TGFβ- and IL-1- dependent expansion of Th9 cells is associated with clinical pathology in human lymphatic filariasis

• Published in: The Journal of immunology (1950) 2013-08, Vol.191 (5), p.2466-2473
• Main Authors: Anuradha, Rajamanickam, George, Parakkal Jovvian, Hanna, Luke E., Chandrasekaran, Vedachalam, Kumaran, Paul, Nutman, Thomas B., Babu, Subash
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1300911

Th9 cells are a subset of CD4 + T cells, shown to be important in allergy, autoimmunity and anti-tumor responses. However, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 co-expressing cells (lacking IL-4 expression) in normal individuals that respond to antigenic and mitogenic stimulation but are distinct from IL-9 + Th2 cells. We also demonstrate that these Th9 cells exhibit antigen –specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial antigen induced Th9 cells but not of IL9 + Th2 cells in comparison to filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared to IL9 + Th2 cells, indicating that the Th9 cells are the predominant CD4 + T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated antigen stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGFβ and IL-1 in vitro. We have therefore a identified an important human CD4 + T cell subpopulation co – expressing IL-9 and IL-10 but not IL-4 that is whose expansion is associated with disease in chronic lymphatic filariasis and could potentially play an important role in the pathogenesis of other inflammatory disorders.