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Rejection of Tumors in Mice with Severe Combined Immunodeficiency Syndrome Determined by the Major Histocompatibility Complex Class I Expression on the Graft¹

Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden

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-2^d) SCID mice were found to reject low (10²) but not high (10⁴) 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 1/2 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 endogeneous 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.

¹ This work was supported by the Swedish Medical Research Council, the Swedish Cancer Society, the Swedish Society for Medicine, and the Karolinska Institute.

² To whom requests for reprints should be addressed.

Received 11/22/94. Accepted 2/10/95.

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