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Published online before print May 3, 2004

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0104038

Received for publication January 23, 2004.
Revised April 4, 2004.
Accepted for publication April 9, 2004.

Article

CD1d-restricted "NKT" cells and myeloid IL-12 production: an immunological crossroads leading to promotion or suppression of effective anti-tumor immune responses?

Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison

^@ To whom correspondence should be addressed. E-mail: jegumperz{at}wisc.edu.

	Abstract

CD1d-restricted T cells are remarkable for their unusual ability to respond to self-antigens and to contribute to T helper cell type 1 (Th1)-oriented "immunostimulatory" and tolerizing or "immunosuppressive" responses. Their effects in different cancer models have appeared contradictory; in some cases, they are linked to the generation of effective tumor clearance, and in others, they seem to contribute to suppression of anti-tumor responses. Recent results suggest CD1d-restricted T cells are involved in critical interactions with myeloid dendritic cells (DCs), which can affect the subsequent course of the immune response, and factors such as the strength of the antigenic signal and the presence or absence of proinflammatory cytokines may determine the outcome of these interactions. In the presence of a strong, antigenic signal, CD1d-restricted T cells induced myeloid DCs to secrete interleukin (IL)-12, and these DCs in turn activated naive T cells to secrete Th1 cytokines. When exposed to the weak, antigenic stimulus of self-antigens, CD1d-restricted T cells induced DCs to secrete IL-10 but not IL-12, and these DCs failed to stimulate Th1 cytokine production by naive T cells. In contrast, CD1d-restricted T cells that were stimulated by self-antigens in the presence of IL-12 potently secreted interferon- (IFN-) and were among the first lymphocytes to become activated in vivo. Hence, CD1d-restricted T cells may promote or prevent effective anti-tumor responses that are mediated by other lymphocytic effector cells by influencing IL-12 production by myeloid DCs and by their own production of early IFN- in response to IL-12.

Key Words: Th1 • IFN- • dendritic cells

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