The innate immune system recognizes and regulates major histocompatibility complex class I (MHCI) expression on MHCIlow tumor cells.
Tumor cells and the immune system play a lethal "pas de deux" during tumor development. However, it is not clear which role the innate immune system plays in these interactions. We studied the interaction of normal spleen cells (NSCs) with tumor cells expressing low levels of MHCI on the cell surface. This interaction induces increased MHCI expression on the MHCI(low) tumor cells by a cell-cell contact-dependent, IFN-gamma-mediated mechanism. The effector cells responsible for the increased IFN-gamma production were identified as CD4+ CD1d-independent NKT cells, NK1.1+ NK cells and CD4+ CD11c+ DCs. The possible three cell collaboration is not activated by MHCI(high) tumor cells or normal fibroblasts. Kinetic experiments showed that the increase in IFN-gamma production induced by MHCI(low) tumor cells happens in two consecutive waves, an early peak around 12 hours, followed by a second more important peak around day 2-3. Thus, we propose that CD4+ CD1d-independent NKT cells are activated by the MHCI(low) tumor cells, they release IFN-gamma stimulating DCs to produce IL-12, which in turn activates NK cells to produce large amounts of IFN-gamma. The recognition mechanism used by the CD4+ CD1d-independent non-classical NKT cells is unknown. Monoclonal antibody (mAb) blocking experiments using antibodies against either activating or inhibitory receptors or co-receptors on NKT/NK cells gave no conclusive results. Moreover, NSCs from either normal or MHCII(-/-) mice augmented MHCI expression on MHCI(low) tumors, excluding a significant role of CD4-MHCII interactions in the system. Hence the initial recognition mechanism in this system still awaits further experimentation.
Rubin
Bent
B
Institut de Sciences et Technologies du Médicament de Toulouse, UMR-2587, CNRS-Pierre Fabre, Toulouse, France. bent.rubin@istmt.cnrs.fr <bent.rubin@istmt.cnrs.fr>
Riond
Joëlle
J
Courtiade
Laetitia
L
Roullet
Nicolas
N
Gairin
Jean-Edouard
JE
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D018949:Antigens, CD1; D015395:Histocompatibility Antigens Class I
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