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


RESULTS
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.
National Institutes of Health-International Center for Excellence in Research, Chennai, India.
Rajamanickam
R
Anuradha
National Institutes of Health-International Center for Excellence in Research, Chennai, India.
Parakkal Jovvian
PJ
George
National Institute for Research in Tuberculosis, Chennai, India.
Luke E
LE
Hanna
National Institute for Research in Tuberculosis, Chennai, India.
Paul
P
Kumaran
National Institute for Research in Tuberculosis, Chennai, India.
Vedachalam
V
Chandrasekaran
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Thomas B
TB
Nutman
National Institutes of Health-International Center for Excellence in Research, Chennai, India; Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Subash
S
Babu
D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004605:Elephantiasis, Filarial / Q000276:immunology*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24; C421250:IL19 protein, human; C406767:IL26 protein, human