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Rejection of kidney allografts by MHC class I-deficient mice.

Publication ,  Journal Article
Mannon, RB; Nataraj, C; Kotzin, BL; Griffiths, R; Geier, S; Ibrahim, S; Sanfilippo, FP; Platt, JL; Kurlander, R; Coffman, TM
Published in: Transplantation
March 15, 1995

To evaluate the requirement for CD8+ T cells in kidney transplant rejection, we studied class I-deficient (class I-) mice that had received vascularized renal allografts. Because of the absence of MHC class I expression, these mice are grossly deficient in CD4-CD8+ alpha beta TCR+ cells. Despite the deficiency of CD8+ T cells in naive class I- mice, kidney allografts transplanted into class I- recipients developed significant reductions in renal blood flow and glomerular filtration rate to levels comparable to allograft controls. This functional deterioration was associated with histologic changes consistent with cellular rejection. There were no significant differences in the pattern, severity, or phenotypic character of the cellular infiltrate in allografts transplanted into class I- recipients compared to controls. In fact, substantial numbers of CD8+ T cells were present in these allografts, and the intensity and pattern of anti-CD8 staining was not different from controls. Virtually all of the CD8+ cells in the kidney grafts were class I- and CD4- and co-expressed CD8 alpha and beta chains; the majority were alpha beta TCR+. The CD8+ infiltrating cells were cytotoxic to donor targets but also exhibited activity against class I+ cells bearing self-MHC. Despite the marked CD8+ T cell infiltration of grafts, CD8+ T cells could not be detected by flow cytometry in freshly isolated splenocytes from the class I- recipients of allografts. High levels of circulating anti-class I antibodies were present in the serum of class I- recipients of kidney allografts, and these antibodies had unusual specificity in that they appeared to recognize framework epitopes of MHC class I. Thus, class I- mice readily reject kidney allografts. Although the number of CD8+ alloreactive precursors is substantially reduced in class mice, and their specificities are atypical, the pattern and character of the intra-graft CD8+ cellular response is not significantly altered. Thus, factors unrelated to precursor frequency determine the dimension of the intra-graft CD8+ response. Such factors might include cellular and/or biochemical properties of microenvironment within the graft.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

March 15, 1995

Volume

59

Issue

5

Start / End Page

746 / 755

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Surgery
  • Phenotype
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Kidney Transplantation
  • Histocompatibility Antigens Class I
  • H-2 Antigens
 

Citation

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MLA
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Mannon, R. B., Nataraj, C., Kotzin, B. L., Griffiths, R., Geier, S., Ibrahim, S., … Coffman, T. M. (1995). Rejection of kidney allografts by MHC class I-deficient mice. Transplantation, 59(5), 746–755. https://doi.org/10.1097/00007890-199503150-00019
Mannon, R. B., C. Nataraj, B. L. Kotzin, R. Griffiths, S. Geier, S. Ibrahim, F. P. Sanfilippo, J. L. Platt, R. Kurlander, and T. M. Coffman. “Rejection of kidney allografts by MHC class I-deficient mice.Transplantation 59, no. 5 (March 15, 1995): 746–55. https://doi.org/10.1097/00007890-199503150-00019.
Mannon RB, Nataraj C, Kotzin BL, Griffiths R, Geier S, Ibrahim S, et al. Rejection of kidney allografts by MHC class I-deficient mice. Transplantation. 1995 Mar 15;59(5):746–55.
Mannon, R. B., et al. “Rejection of kidney allografts by MHC class I-deficient mice.Transplantation, vol. 59, no. 5, Mar. 1995, pp. 746–55. Pubmed, doi:10.1097/00007890-199503150-00019.
Mannon RB, Nataraj C, Kotzin BL, Griffiths R, Geier S, Ibrahim S, Sanfilippo FP, Platt JL, Kurlander R, Coffman TM. Rejection of kidney allografts by MHC class I-deficient mice. Transplantation. 1995 Mar 15;59(5):746–755.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

March 15, 1995

Volume

59

Issue

5

Start / End Page

746 / 755

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Surgery
  • Phenotype
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Kidney Transplantation
  • Histocompatibility Antigens Class I
  • H-2 Antigens