Novel CD8 T cell alloreactivities in CCR5-deficient recipients of class II MHC disparate kidney grafts

Daisuke Ishii, Joshua M. Rosenblum, Taiji Nozaki, Austin D. Schenk, Kiyoshi Setoguchi, Charles A. Su, Victoria Gorbacheva, William M. Baldwin, Anna Valujskikh, Robert L. Fairchild

Research output: Contribution to journalArticle

Abstract

Recipient CD4 T regulatory cells inhibit the acute T cell-mediated rejection of renal allografts in wild-type mice. The survival of single class II MHC-disparate H-2bm12renal allografts was tested in B6.CCR5-/-recipients, which have defects in T regulatory cell activities that constrain alloimmune responses. In contrast to wild-type C57BL/6 recipients, B6.CCR5-/-recipients rejected the bm12 renal allografts. However, donor-reactive CD8 T cells rather than CD4 T cells were the primary effector T cells mediating rejection. The CD8 T cells induced to bm12 allografts in CCR5-deficient recipients were reactive to peptides spanning the 3 aa difference in the I-Abm12versus I-Ab b-chains presented by Kb and Db class I MHC molecules. Allograft-primed CD8 T cells from CCR5-deficient allograft recipients were activated during culture either with proinflammatory cytokine-stimulated wild-type endothelial cells pulsed with the I-Abm12peptides or with proinflammatory cytokine-simulated bm12endothelial cells, indicating their presentation of the I-Abm12b-chain peptide/class I MHC complexes. In addition to induction by bm12renal allografts, the I-Abm12b-chain-reactive CD8 T cells were induced in CCR5-deficient, but not wild-type C57BL/6, mice by immunization with the peptides. These results reveal novel alloreactive CD8 T cell specificities in CCR5-deficient recipients of single class II MHC renal allografts that mediate rejection of the allografts.

Original languageEnglish (US)
Pages (from-to)3816-3824
Number of pages9
JournalJournal of Immunology
Volume193
Issue number7
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Ishii, D., Rosenblum, J. M., Nozaki, T., Schenk, A. D., Setoguchi, K., Su, C. A., Gorbacheva, V., Baldwin, W. M., Valujskikh, A., & Fairchild, R. L. (2014). Novel CD8 T cell alloreactivities in CCR5-deficient recipients of class II MHC disparate kidney grafts. Journal of Immunology, 193(7), 3816-3824. https://doi.org/10.4049/jimmunol.1303256