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

Babu, Subash and Kumaraswami, V and Nutman, T B (2005) Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes. Infection and Immunology, 73 (6). pp. 3394-3401. ISSN Print: 0019-9567; Online: 1098-5522

Preview

PDF
200503.pdf - Published Version
Download (317kB)

Official URL: http://iai.asm.org/content/73/6/3394.full.pdf+html

Abstract

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-�) 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-� 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, parasitespecific 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.

Item Type:	Article
Subjects:	Filariasis
Divisions:	Clinical Research
Depositing User:	Dr. Rathinasabapati R
Date Deposited:	22 Nov 2013 11:19
Last Modified:	09 Mar 2016 06:59
URI:	http://eprints.nirt.res.in/id/eprint/682

Actions (login required)

View Item