Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

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

Publication ,  Journal Article
Coffman, T; Geier, S; Ibrahim, S; Griffiths, R; Spurney, R; Smithies, O; Koller, B; Sanfilippo, F
Published in: J Immunol
July 1, 1993

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 beta 2 microglobulin (beta 2m) 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.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

July 1, 1993

Volume

151

Issue

1

Start / End Page

425 / 435

Location

United States

Related Subject Headings

  • Time Factors
  • Mice
  • Kidney Transplantation
  • Kidney
  • Isoantigens
  • Isoantibodies
  • Immunology
  • Immunity, Cellular
  • Histocompatibility Antigens Class I
  • Chimera
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Coffman, T., Geier, S., Ibrahim, S., Griffiths, R., Spurney, R., Smithies, O., … Sanfilippo, F. (1993). Improved renal function in mouse kidney allografts lacking MHC class I antigens. J Immunol, 151(1), 425–435.
Coffman, T., S. Geier, S. Ibrahim, R. Griffiths, R. Spurney, O. Smithies, B. Koller, and F. Sanfilippo. “Improved renal function in mouse kidney allografts lacking MHC class I antigens.J Immunol 151, no. 1 (July 1, 1993): 425–35.
Coffman T, Geier S, Ibrahim S, Griffiths R, Spurney R, Smithies O, et al. Improved renal function in mouse kidney allografts lacking MHC class I antigens. J Immunol. 1993 Jul 1;151(1):425–35.
Coffman, T., et al. “Improved renal function in mouse kidney allografts lacking MHC class I antigens.J Immunol, vol. 151, no. 1, July 1993, pp. 425–35.
Coffman T, Geier S, Ibrahim S, Griffiths R, Spurney R, Smithies O, Koller B, Sanfilippo F. Improved renal function in mouse kidney allografts lacking MHC class I antigens. J Immunol. 1993 Jul 1;151(1):425–435.

Published In

J Immunol

ISSN

0022-1767

Publication Date

July 1, 1993

Volume

151

Issue

1

Start / End Page

425 / 435

Location

United States

Related Subject Headings

  • Time Factors
  • Mice
  • Kidney Transplantation
  • Kidney
  • Isoantigens
  • Isoantibodies
  • Immunology
  • Immunity, Cellular
  • Histocompatibility Antigens Class I
  • Chimera