Signaling through the T1/ST2 molecule is not necessary for Th2 differentiation but is important for the regulation of type 1 responses in nonhealing Leishmania major infection.


Kropf, P; Herath, S; Klemenz, R; Müller, I; (2003) Signaling through the T1/ST2 molecule is not necessary for Th2 differentiation but is important for the regulation of type 1 responses in nonhealing Leishmania major infection. Infection and immunity, 71 (4). pp. 1961-71. ISSN 0019-9567 DOI: https://doi.org/10.1128/IAI.71.4.1961-1971.2003

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Abstract

T1/ST2 is a stable cell surface marker selectively expressed on type 2 T helper (Th2) effector cells. Since nonhealing Leishmania major infections in susceptible BALB/c mice have been ascribed to a polarized Th2 response, we used an anti-T1/ST2 monoclonal antibody (MAb) or a T1-Fc fusion protein to investigate the role of CD4+ T1/ST2(+) Th2 cells in experimental leishmaniasis. We show that interfering with T1/ST2 signaling had no effect on lesion development or parasite replication; however, it induced a significantly higher type 1 response and an enhanced capacity of CD4+ T cells to respond to interleukin 12 (IL-12). Surprisingly, even in the presence of an elevated Th1 response, the production of antigen-specific type 2 cytokines was not altered in the group of mice treated with the anti-T1/ST2 MAb or the T1-Fc fusion protein. To characterize further this Th2 response, we assessed the cytokine profile of CD4+ T cells and found that interfering with T1/ST2 signaling did not alter the cytokine profile of CD4+ T1/ST2(+) T cells. These results show that T1/ST2 signaling is not necessary for the differentiation of naive CD4+ T cells into antigen-specific CD4+ T1/ST2(+) Th2 cells. In addition to CD4+ T1/ST2(+) T cells, we detected another subpopulation of CD4+ Th2 cells, negative for the expression of T1/ST2, that could differentiate in vivo in response to L. major infection. Taken together, our results suggest that CD4+ T1/ST2(+) Th2 cells but not CD4+ T1/ST2(-) Th2 cells can downregulate the Th1 response during the course of a nonhealing L. major infection through a mechanism that is independent of IL-4 or IL-10.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
PubMed ID: 12654814
Web of Science ID: 181926200043
URI: http://researchonline.lshtm.ac.uk/id/eprint/1627

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