title: Regulation of CD1d expression by murine tumor cells: escape from immunosurveillance or alternate target molecules?
abstract: alpha beta+ 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 V alpha 14 J alpha 281 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-gamma), 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-gamma release. Thus, modulation of CD1 expression on tumor cells by cytokines may be advantageous to drive cellular anti-tumor antigen directed immune responses directed against TAP-independent, non-classical MHC restricting molecules.
authors.affiliation: Department of Medical Microbiology, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Fiedler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Walter
authors.forename: Torsten E
authors.initials: TE
authors.lastname: Reichert
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D018949:Antigens, CD1 / Q000235:genetics* / Q000378:metabolism; D055610:Antigens, CD1d; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015166:Monitoring, Immunologic; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor