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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

404 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
Pages (from-to)465-474
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • Depletion
  • Immunosuppression
  • T cell
  • Transplantation

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