Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion

Jonathan P. Pearl, Jeremy Parris, Douglas A. Hale, Steven C. Hoffmann, Wendy B. Bernstein, Kelly L. McCoy, S. John Swanson, Roslyn B. Mannon, Mario Roederer, Allan D. Kirk

Research output: Contribution to journalArticle

373 Scopus citations

Abstract

T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We therefore studied patients undergoing profound T-cell depletion with alemtuzumab or rabbit anti-thymocyte globulin following renal transplantation, evaluating the phenotype and functional characteristics of their residual cells. Naïve T cells and T cells with potential regulatory function (CD4+CD25+) were not prevalent following aggressive depletion. Rather, post-depletion T cells were of a single phenotype (CD3+CD4+CD45RA-CD62L-CCR7-) consistent with depletion-resistant effector memory T cells that expanded in the first month and were uniquely prevalent at the time of rejection. These cells were resistant to steroids, deoxyspergualin or sirolimus in vitro, but were calcineurin-inhibitor sensitive. These data demonstrate that therapeutic depletion begets a limited population of functional memory-like T cells that are easily suppressed with certain imrnunosuppressants, but cannot be considered uniquely pro-tolerant.

Original languageEnglish (US)
Pages (from-to)465-474
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Depletion
  • Immunosuppression
  • T cell
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Pearl, J. P., Parris, J., Hale, D. A., Hoffmann, S. C., Bernstein, W. B., McCoy, K. L., Swanson, S. J., Mannon, R. B., Roederer, M., & Kirk, A. D. (2005). Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. American Journal of Transplantation, 5(3), 465-474. https://doi.org/10.1111/j.1600-6143.2005.00759.x