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Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway.

Publication ,  Journal Article
Wang, L; Han, R; Lee, I; Hancock, AS; Xiong, G; Gunn, MD; Hancock, WW
Published in: J Immunol
November 15, 2005

Chemokine receptor blockade can diminish the recruitment of host effector cells and prolong allograft survival, but little is known of the role of chemokine receptors in promoting host sensitization. We engrafted fully allogeneic islets into streptozotocin-treated normal mice or mice with the autosomal recessive paucity of lymph node T cell (plt) mutation; the latter lack secondary lymphoid expression of the CCR7 ligands, secondary lymphoid organ chemokine (CCL21) and EBV-induced molecule-1 ligand chemokine (CCL19). plt mice showed permanent survival of islets engrafted under the kidney capsule, whereas controls rejected islet allografts in 12 days (p < 0.001), and consistent with this, plt mice had normal allogeneic T cell responses, but deficient migration of donor dendritic cell to draining lymph nodes. Peritransplant i.v. injection of donor splenocytes caused plt recipients to reject their allografts by 12 days, and sensitization at 60 days posttransplant of plt mice with well-functioning allografts restored acute rejection. Finally, islet allografts transplanted intrahepatically in plt mice were rejected approximately 12 days posttransplant, like controls, as were primarily revascularized cardiac allografts. These data show that the chemokine-directed homing of donor dendritic cell to secondary lymphoid tissues is essential for host sensitization and allograft rejection. Interruption of such homing can prevent T cell priming and islet allograft rejection despite normal T and B cell functions of the recipient, with potential clinical implications.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

November 15, 2005

Volume

175

Issue

10

Start / End Page

6311 / 6318

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes
  • Receptors, Chemokine
  • Receptors, CCR7
  • Mice, Mutant Strains
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Major Histocompatibility Complex
 

Citation

APA
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ICMJE
MLA
NLM
Wang, L., Han, R., Lee, I., Hancock, A. S., Xiong, G., Gunn, M. D., & Hancock, W. W. (2005). Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway. J Immunol, 175(10), 6311–6318. https://doi.org/10.4049/jimmunol.175.10.6311
Wang, Liqing, Rongxiang Han, Iris Lee, Aidan S. Hancock, Guoxiang Xiong, Michael D. Gunn, and Wayne W. Hancock. “Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway.J Immunol 175, no. 10 (November 15, 2005): 6311–18. https://doi.org/10.4049/jimmunol.175.10.6311.
Wang L, Han R, Lee I, Hancock AS, Xiong G, Gunn MD, et al. Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway. J Immunol. 2005 Nov 15;175(10):6311–8.
Wang, Liqing, et al. “Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway.J Immunol, vol. 175, no. 10, Nov. 2005, pp. 6311–18. Pubmed, doi:10.4049/jimmunol.175.10.6311.
Wang L, Han R, Lee I, Hancock AS, Xiong G, Gunn MD, Hancock WW. Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway. J Immunol. 2005 Nov 15;175(10):6311–6318.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

November 15, 2005

Volume

175

Issue

10

Start / End Page

6311 / 6318

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes
  • Receptors, Chemokine
  • Receptors, CCR7
  • Mice, Mutant Strains
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Major Histocompatibility Complex