The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 14 April 2003 doi:10.1084/jem.20021616
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© Rockefeller University Press, 0022-1007/2003/4/1051 $5.00
The Journal of Experimental Medicine, Volume 197, Number 8, 1051-1057

Brief Definitive Report

CD1d-restricted Help To B Cells By Human Invariant Natural Killer T Lymphocytes

Grazia Galli1, Sandra Nuti1, Simona Tavarini1, Luisa Galli-Stampino1, Claudia De Lalla2, Giulia Casorati2, Paolo Dellabona2 and Sergio Abrignani1

1 IRIS Research Center, Chiron Vaccines, 53100 Siena, Italy
2 Cancer Immunotherapy and Gene Therapy Program DIBIT, H. San Raffaele Scientific Institute, 20132 Milano, Italy

Address correspondence to Sergio Abrignani, IRIS Research Center, Chiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy. Phone: 39-0577-243032; Fax: 39-0577-243564; E-mail: sergio_abrignani{at}chiron.com; or Paolo Dellabona, DIBIT, H. San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. Phone: 39-02-26434727; Fax: 39-02-26434786; E-mail: dellabona.paolo{at}hsr.it

Invariant natural killer T (NKT) cells are a highly conserved subset of T lymphocytes expressing a semi-invariant T cell receptor (TCR), which is restricted to CD1d and specific for the glycosphingolipid antigen {alpha}-galactosylceramide. Their ability to secrete a variety of cytokines, which in turn modulate the activation of cells of both innate and acquired immune responses, suggests that invariant NKT cells exert a regulatory role mainly via indirect mechanisms. A relevant question is whether invariant NKT cells can directly help B cells. We document here that human invariant NKT cells are as efficient as conventional CD4+ Th0 lymphocytes in promoting proliferation of autologous memory and naive B lymphocytes in vitro, and in inducing immunoglobulin production. Help to B cells by invariant NKT cells is CD1d-dependent and delivered also in the absence of {alpha}-galactosylceramide, suggesting that NKT cells recognize an endogenous ligand presented by CD1d on B cells. The two major subsets of invariant NKT cells, CD4+ and double negative (CD4-CD8-), express comparable levels of CD40 ligand and cytokines, but differ in helper functions. Indeed, both subsets induce similar levels of B cell proliferation, whereas CD4+ NKT cells induce higher levels of immunoglobulin production. These results suggest a direct role for invariant NKT cells in regulating B lymphocyte proliferation and effector functions.

Key Words: autoreactivity • cytokine • {alpha}-galactosylceramide • antibodies • helper assay


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