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Infection and Immunity, June 2005, p. 3394-3401, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3394-3401.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes

Subash Babu,1* V. Kumaraswami,2 and Thomas B. Nutman1

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,1 Tuberculosis Research Center, Chennai, India2

Received 17 November 2004/ Returned for modification 4 January 2005/ Accepted 20 January 2005

T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (n = 6) and uninfected controls (n = 6). As expected (and in contrast to cells of uninfected individuals), there was a significant depression of gamma interferon (IFN-{gamma}) and a concomitant increase in interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected group, accounting, at least partially, for the diminished IFN-{gamma} expression. Second, we found no significant differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasite-specific T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1 responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1, SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells.

* Corresponding author. Mailing address: LPD, NIAID, 4 Center Drive, Room 4/B1-05, NIH, Bethesda, MD 20892-0425. Phone: (301) 435-8649. Fax: (301) 480-3757. E-mail: sbabu{at}niaid.nih.gov.

Editor: J. F. Urban, Jr.

Infection and Immunity, June 2005, p. 3394-3401, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3394-3401.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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