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

• Published in: PLoS neglected tropical diseases 2014-04, Vol.8 (4)
• Main Authors: Anuradha, Rajamanickam, George, Parakkal Jovvian, Hanna, Luke E, Kumaran, Paul, Chandrasekaran, Vedachalam, Nutman, Thomas B, Babu, Subash
• Format: Article
• Language: English
• Subjects: Cytokines; Filariasis; Genetic aspects; Genetic regulation; Physiological aspects; T cells
• ISSN: 1935-2727
• DOI: 10.1371/journal.pntd.0002762

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/PrincipalFindings: We examined the expression patterns of IL-10 family members--IL-19, IL-24 and IL-26 in LF. We demonstrate that both [CD4.sup.+] and [CD8.sup.+] T cells express IL-19, IL-24 and IL-26 and that the frequency of [CD4.sup.+] 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.sup.+] 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.sup.+] and [CD8.sup.+] 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.sup.+] and [IL-24.sup.+] T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of [IL-19.sup.+] and [IL-24.sup.+] 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[beta] and IL-23 blockade also induced a diminution in the frequency of [IL-19.sup.+] and [IL-24.sup.+] 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.sup.+] 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.