Rejection of tumors in mice with severe combined immunodeficiency syndrome determined by the major histocompatibility complex. Class I expression on the graft
Glas, R.; Waldenström, M.; Höglund, P.; Klein, G.; Kärre, K.; Ljunggren, H.G.
Cancer Research 55(9): 1911-1916
1995
ISSN/ISBN: 0008-5472 PMID: 7728758 Document Number: 452940
This study addresses the role of MHC class I molecules in the rejection of tumor grafts by SCID mice. Tumor cell fines, their corresponding MHC class I transfectants, and MHC class I-deficient mutants were inoculated to SCID mice. This allowed a study of tumor rejection responses in an environment with normal numbers of natural killer cells but largely devoid of functional T and B cells. C.B-17 (H-2-d) SCID mice were found to reject low (10-2) but not high (10-4) doses of allogeneic (H-2-b) tumor cells. The introduction of H-2D-d into such allogeneic tumor cells abrogated the rejection response with progressive tumor growth as a consequence. Introduction of H-2K-d or L-d had no or only marginal effects. The protective ability of H-2D-d was mapped to the alpha-1/alpha-2 domains of the molecule. H-2D-d protected allogeneic tumors from rejection also in C3H SCID mice of the H-2-k haplotype, demonstrating that this ability was not dependent on H-2D-d expression in the host. Expression of endogenous H-2K-b and/or D-b molecules partially protected wild-type allogeneic tumor cells from rejection since mutant allogeneic cells, devoid of class I expression, were rejected even after high-dose inoculation. Introduction of either allogeneic or xenogeneic class I molecules did not lead to rejection of otherwise MHC class I syngeneic (H-2-d) tumor cells. The observed tumor cell rejection in SCID mice was dependent on natural killer cells. After depletion of asialo-GM1+ cells, all inoculated tumor cell lines grew progressively, independently of MHC class I expression. These results are compatible with a model where expression of certain, but not all, class I molecules protect from natural killer cell-mediated rejection. There was no evidence for rejection occurring as a consequence of the expression of allogeneic or xenogeneic class I molecules on the grafted cells. MHC class I expression may thus influence tumor cell recognition in mice lacking T-cell receptor expression.