Improved renal function in mouse kidney allografts lacking MHC class I antigens

Thomas Coffman, Steven Geier, Sherif Ibrahim, Robert Griffiths, Robert Spurney, Oliver Smithies, Beverly Koller, Fred Sanfilippo

Research output: Contribution to journalArticle

Abstract

The immunological responses that lead to rejection of organ and tissue transplants are triggered by the recognition of proteins encoded within the MHC. The relative contributions of responses directed toward MHC class I compared with class II in the loss of functional integrity of vascularized organ grafts have been difficult to define. The recent development of technologies which allow the generation of mice in which specific genes have been altered by gene targeting offers a new approach to addressing this question. We examine here the rejection of kidney allografts from mice lacking native MHC class I Ag. These mice were obtained from embryonic stem cells in which the β2 microglobulin (β2m) gene had been disrupted by homologous recombination. We found a significant improvement in function of renal allografts from MHC class I-deficient donors compared with allografts from donors with normal MHC class I expression. Surprisingly, the improved function of the MHC class I-deficient grafts was not associated with differences in mononuclear inflammatory cell infiltration of these grafts nor in differences in alloreactive proliferative or cytotoxic T cell responses. However, we did find differences in alloantibody response between the groups. Recipients of control allografts produced antibodies against both donor MHC class I and II, whereas recipients of MHC class I-deficient grafts formed alloantibodies primarily against donor MHC class II Ag. These studies confirm that immune responses directed toward donor MHC class I alloantigens contribute to kidney transplant dysfunction in this model. Also, these findings suggest that, at least for renal transplants, genetic manipulations which reduce MHC class I expression may be effective in overcoming some of the effects of MHC incompatibility.

Original languageEnglish (US)
Pages (from-to)425-435
Number of pages11
JournalJournal of Immunology
Volume151
Issue number1
StatePublished - Jul 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Coffman, T., Geier, S., Ibrahim, S., Griffiths, R., Spurney, R., Smithies, O., Koller, B., & Sanfilippo, F. (1993). Improved renal function in mouse kidney allografts lacking MHC class I antigens. Journal of Immunology, 151(1), 425-435.