Rejection of tumors in mice with severe combined immunodeficiency syndrome determined by the major histocompatibility complex class I expression on the graft

• Published in: Cancer research (Chicago, Ill.) Ill.), 1995-05, Vol.55 (9), p.1911-1916
• Main Authors: GLAS, R, WALDENSTRÖM, M, HÖGLUND, P, KLEIN, G, KÄRRE, K, LJUNGGREN, H.-G
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; B-Lymphocytes - immunology; Biological and medical sciences; G(M1) Ganglioside - pharmacology; Graft Rejection - immunology; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; HLA-A2 Antigen - genetics; HLA-A2 Antigen - immunology; Killer Cells, Natural - immunology; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, SCID; Mutation; Neoplasm Transplantation; Neoplasms, Experimental - immunology; Severe Combined Immunodeficiency - immunology; T-Lymphocytes - immunology; Transfection; Transplantability; Tumor cell; Tumor Cells, Cultured; Tumors
• ISSN: 0008-5472; 1538-7445

This study addresses the role of MHC class I molecules in the rejection of tumor grafts by SCID mice. Tumor cell lines, 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-2d) SCID mice were found to reject low (10(2)) but not high (10(4)) doses of allogeneic (H-2b) tumor cells. The introduction of H-2Dd into such allogeneic tumor cells abrogated the rejection response with progressive tumor growth as a consequence. Introduction of H-2Kd or Ld had no or only marginal effects. The protective ability of H-2Dd was mapped to the alpha 1/alpha 2 domains of the molecule. H-2Dd protected allogeneic tumors from rejection also in C3H SCID mice of the H-2k haplotype, demonstrating that this ability was not dependent on H-2Dd expression in the host. Expression of endogenous H-2Kb and/or Db 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-2d) 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.