Expansion of Parasite-Specific CD4+ and CD8+ T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis: e2762

• 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: Antigens; Bacterial infections; Cytokines; Disease; Expansion; Gene expression; Infections; Lymphocytes; Parasites; Pathogenesis; Pathology; Studies; Tropical diseases; Vector-borne diseases
• ISSN: 1935-2727; 1935-2735
• 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/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-1β 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.