International Immunology, Vol. 13, No. 4, 431-439,
April 2001
© 2001 Japanese Society for Immunology
Chronic exposure to superantigen induces regulatory CD4+ T cells with IL-10-mediated suppressive activity
1 Laboratory of Experimental Immunology, Université Libre de Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium
2 Service de Néphrologie, CHRU-Lille, 59037 Lille, France
3 Department of Pathology, AMC, NL-1100 Amsterdam, The Netherlands
Correspondence to: M. Y. Braun
The repeated injection of bacterial superantigens (SAg), such as staphylococcus enterotoxin (SE) A or B, has been shown in mice to induce a state of unresponsiveness characterized by the lack of secretion of Th1 lymphokines, such as IL-2 and IFN-
, following subsequent SAg challenge. We made the observation, in vivo as well as in vitro, that unresponsiveness to SAg could be transferred from SEA- to SEB-reactive T cells (and reversibly from SEB- to SEA-specific T cells) in C57BL/6 mice but not in BALB/c mice. Since C57BL/6 mice, unlike BALB/c mice, possess TCR Vß3+ and Vß11+ T cells able to react with both SEA and SEB, we hypothesized that SAg-unresponsive Vß3+ and Vß11+ T cells could mediate linked suppression of other SAg-reactive T cells. To analyze further this possibility, spleen cells from BALB/c mice made unresponsive to SEB were tested for their capacity to suppress the response of normal BALB/c cells to SEB. The production of both IFN- and IL-2 following SEB stimulation was greatly impaired in co-cultures containing CD4+ T cells, but not CD8+ T cells, isolated from unresponsive animals. In vivo, the production of both IFN- and IL-2 responses to SEB was dramatically reduced in animals adoptively transferred with unresponsive spleen cells. This suppression was abrogated in recipients injected with neutralizing anti-IL-10 antibodies. Moreover, in animals made unresponsive to SEB, SAg-reactive CD4+ T cells were found to express high levels of CTLA-4, a molecule recently described to play an essential role in the suppressive function of regulatory T cells. Taken together these results demonstrate that the repetitive injection of SAg induces the differentiation of regulatory CD4+ T cells capable of suppressing SAg-reactive naive T cells.
Keywords: anergy, CTLA-4, IL-10, suppression
Transmitting editor: J.-F. Bach
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