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Immunocompetent T‐Cells with a Memory‐Like Phenotype are the Dominant Cell Type Following Antibody‐Mediated T‐Cell Depletion
Author(s) -
Pearl Jonathan P.,
Parris Jeremy,
Hale Douglas A.,
Hoffmann Steven C.,
Bernstein Wendy B.,
McCoy Kelly L.,
Swanson S. John,
Man Roslyn B.,
Roederer Mario,
Kirk Allan D.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00759.x
Subject(s) - il 2 receptor , calcineurin , immunology , cd28 , transplantation , t cell , alemtuzumab , phenotype , population , interleukin 7 receptor , cd3 , thymocyte , medicine , effector , microbiology and biotechnology , biology , antibody , cd8 , immune system , environmental health , gene , biochemistry
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 immunosuppressants, but cannot be considered uniquely pro‐tolerant.