Regulation of CD1d expression by murine tumor cells: Escape from immunosurveillance or alternate target molecules?

Abstract

αβ+ TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1d1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or "natural T cells" with the invariant Vα14 Jα281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. Therefore, CD1-mediated recognition of transformed cells by NK cells or "natural T cells" may represent an alternative way for immune surveillance. CD1 cell surface expression in murine tumor cell lines of different histology, including the B cell lymphoma A20, macrophage cell lines J774 and P388D1, mastocytoma P815, thymoma EL-4, melanoma B16, colon adenocarcinoma MC-38 and renal carcinoma Renca is regulated by Th1- (IFN-γ), Th2- (IL-4, IL-10 and vIL-10) or GM-CSF (Th1/Th2) cytokines, depending on the tumor histology. In order to distinguish between CD1d1 and CD1d2 molecules, we examined differential expression of these CD1 isoforms by ratio RT-PCR: A20, EL-4, P815 and MC-38 cells exclusively express CD1D1 transcripts but not CD1D2 mRNA independent of cytokine treatment. Decreased CD1d expression leads to reduced immune recognition of CD1d+ tumor cells by freshly isolated NK1.1+ effector cells as defined by cytolysis and IFN-γ release. Thus, modulation of CD1 expression on tumor cells by cytokines may be advantageous to drive cellular antitumor antigen directed immune responses directed against TAP-independent, non-classical MHC restricting molecules. © 2002 Wiley-Liss, Inc.