Interpreting NK Cell Transcripts Versus T Cell Transcripts in Renal Transplant Biopsies

Authors

  • L. G. Hidalgo,

    1. Department of Laboratory Medicine and Pathology, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada
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  • J. Sellares,

    1. Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada
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  • B. Sis,

    1. Department of Laboratory Medicine and Pathology, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada
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  • M. Mengel,

    1. Department of Laboratory Medicine and Pathology, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada
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  • J. Chang,

    1. Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada
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  • P. F. Halloran

    Corresponding author
    1. Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada
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Corresponding author: Philip F. Halloran, phil.halloran@ualberta.ca

Abstract

NK cell transcripts are increased in biopsies with antibody-mediated rejection, whereas T cell transcripts are increased in T cell-mediated rejection. However, NK and T cells share many features, creating potential ambiguity. Therefore to estimate the NK- versus T cell transcript burdens separately, we defined nonoverlapping transcripts selective for NK cells (N = 4) or T cells (N = 5). We compared NK- versus T cell transcript burdens in microarrays from 403 kidney transplant biopsies (182 early, 221 late). In late biopsies, high NK-cell transcript expression was associated with antibody-mediated rejection, correlating with microvascular inflammation and donor specific HLA antibody. However, some early biopsies with T cell-mediated rejection had high NK-cell transcript expression, as well as T cell transcripts, without evidence of antibody-mediated rejection or DSA, correlating with interstitial inflammation and tubulitis. Both NK-cell and T cell transcripts were moderately increased in many kidneys with inflammation secondary to injury or atrophy scarring. These results support the distinct role of NK cells in late antibody-mediated rejection, but indicate a role for NK-transcript expressing cells (NK cells or T cells with NK features) both in T cell-mediated rejection and in inflammation associated with injury and atrophy scarring.

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