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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1007669

Received for publication October 4, 2007.
Revised March 20, 2008.
Accepted for publication March 26, 2008.

Article

IL-2 triggers specific signaling pathways in human NKT cells leading to the production of pro- and anti-inflammatory cytokines

Stéphanie Bessoles *, Frédéric Fouret *, Sherri Dudal *, Gurdyal S. Besra {dagger}, Françoise Sanchez *, and Virginie Lafont *@

*Université Montpellier 1, Centre d’étude d’agents Pathogènes et Biotechnologies pour la Santé, CNRS UMR 5236, Montpellier, France; and {dagger}School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom

@ To whom correspondence should be addressed. E-mail: vlafont{at}crit.univ-montp2.fr.


  Abstract

NKT cells belong to a conserved T lymphocyte subgroup that has been implicated in the regulation of various immune responses, including responses to viruses, bacteria, and parasites. They express a semi-invariant TCR that recognizes glycolipids presented by the nonpolymorphic MHC class I-like molecule CD1d, and upon activation, they produce various pro- and anti-inflammatory cytokines. Recent studies have shed light on the nature of glycolipids and the environmental signals that may influence the production of cytokines by NKT cells and thus, modulate the immune response. To better understand the regulation mechanisms of NKT cells, we explored their behavior following activation by IL-2 and investigated the signaling pathways and biological responses triggered. We demonstrated that IL-2 activates not only STAT3 and -5 and the PI-3K and ERK-2 pathways as in all IL-2 responder cells but also STAT4 as in NK cells and the p38 MAPK pathway as in {alpha}{beta} T cells. We also showed that STAT6 is activated by IL-2 in NKT cells. Moreover, IL-2 induces the production of IFN-{gamma} and IL-4. The ability of IL-2 to induce pro- and anti-inflammatory cytokine production, in addition to proliferation, could open new therapeutic approaches for use in combination with molecules that activate NKT cells through TCR activation.

Key Words: nonconventional lymphocytes • STAT






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