CD8⁺ CD26⁺⁺ Lymphocytes Are T Memory Cells with T Cell Repopulating Capacity and Are Depleted in the Course of Haematopoietic Progenitor Cell Aphaeresis

Abstract 2989

The glycoprotein dipeptidyl peptidase IV (DPP IV, CD26) possesses an enzymatic activity which is crucial for the turnover of chemokines including CCL5/RANTES, CXCL12/SDF-1a, CCL8/MCP-2 and CCL11/Eotaxin. CD26 is primarily expressed on subsets of human lymphocytes as well as on murine splenocytes, thymocytes and decidual lymphocytes. A subpopulation of memory T cells shows a high surface expression of CD26 that has been shown to be related to resolved viral infections, production of interleukin-2, and tissue invasion. Furthermore, CD26 affects the turnover of adenosine, since human CD26 anchors adenosine deaminase (ADA) to the lymphocyte surface.

We had shown previously that, in the course of haematopoietic progenitor cell (HPC) aphaeresis, a distinct subset of CD8⁺CD26⁺⁺ lymphocytes was enriched in the aphaeresis products to a varying extent. High numbers of these cells in HPC autografts were associated with a poor clinical outcome after autologous HPC transplantation. A phenotypic characterization of CD26⁺⁺ cells was performed with samples of peripheral blood from healthy donors using multicolor flow cytometric analysis.

The characterization of CD26⁺⁺/CD8⁺ cells identified these cells as a homogeneous population with a distinct T memory cell phenotype (CD45RO⁺, CD161⁺⁺, IL18Ralpha⁺⁺, CCR7⁻), consistent with a population of T cells with high rhodamine efflux, chemoresistance and T cell repopulating capacity described before. Conversely, gating of CD45RO⁺, CD161⁺⁺, IL18Ralpha⁺⁺, CCR7⁻ cells yielded a population of cells that were exclusively CD8⁺ and CD26⁺⁺.

We conclude that CD8⁺ CD26⁺⁺ cells define T memory cells with chemoresistance and repopulating capacity as defined by the phenotype: CD45RO⁺ CD161⁺⁺ IL18Ralpha⁺⁺ CCR7⁻. The observation that the enrichment of these cells in the course of progenitor cell apheresis is associated with poor clinical outcome after PBSCT could be explained by a depletion of these cells from the peripheral blood which could be hazardous. Technical improvements of the apheresis procedure are feasible. Furthermore, the characterization of T memory cells with repopulating capacity as CD8⁺ CD26⁺⁺ allows a simple approach for their isolation fur further processing. The quantification of CD8⁺ CD26⁺⁺ cells has now been integrated into the routine immunomonitoring to further assess this facet of post-transplantation immune reconstitution and possible correlations with the clinical course after allogeneic stem cell transplantation.