Expansion of parasite-specific CD4 + and CD8 + T cells expressing IL-10 superfamily cytokine members and their regulation in human lymphatic filariasis.

Anuradha, R.; George, P.J.; Hanna, L.E.; Kumaran, P.P.; Chandrasekaran, V.; Nutman, T.B.; Babu S .

PLoS Neglected Tropical Diseases; 2014; 8: e2762.

Summary: Setting: National Institute for Research in Tuberculosis , India .

Abstract: Background: Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known.

Methodology/Principal Findings: We examined the expression patterns of IL-10 family members – IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4 + and CD8 + T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4 + T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4 + T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial – antigen stimulated PBMC. Moreover, the frequency of CD4 + and CD8 + T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19 + and IL-24 + T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19 + and IL-24 + T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1 b and IL-23 blockade also induced a diminution in the frequency of IL-19 + and IL-24 + T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen – specific CD4 + T cells expressing IL-10, IL-19 and IL-24.

Conclusions: Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF.

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