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BACKGROUND: The lymphocyte surface glycoprotein CD26 anchors adenosine deaminase to the lymphocyte surface and possesses dipeptidyl peptidase IV activity. A distinct subset of CD26++ lymphocytes in autologous hematopoietic progenitor cell transplants (HPCTs) was investigated with regard to clinical outcome after autologous HPCT. The phenotype of these cells was characterized in more detail. STUDY DESIGN AND METHODS: Forty-two eligible patients (multiple myeloma, n = 31; Hodgkin's disease, n = 3; non-Hodgkin's lymphoma, n = 6; peripheral neuroectodermal tumor, n = 1; acute myeloid leukemia, n = 1) were included in a retrospective analysis. Distinct cellular subsets, including CD26+/− and CD26++ subpopulations, were analyzed for correlations with kinetics of engraftment, progression-free survival, and overall survival. RESULTS: The numbers of CD26++ T lymphocytes in the autograft correlated inversely with progression-free survival (p = 0.013). CD26++ T lymphocytes transfused per kg of body weight were predictive for the occurrence of disease progression or relapse (p = 0.006). Importantly, the numbers of CD26++ cells showed a highly variable degree of enrichment in the autograft, but no significant variations in the peripheral blood before apheresis. The characterization of CD26++ cells revealed that CD26++/CD8+ cells form a homogeneous population with a distinct T memory cell phenotype (CD45RO+, CD161++, interleukin-18Rα++, CCR7−). CONCLUSION: CD26++ lymphocytes define a discrete phenotype of T memory cells with known chemoresistance and T-cell-repopulating capacity. Their enrichment during apheresis and corresponding depletion from the circulation are associated with an adverse outcome in autologous HPCT.

To explore phenotype and function of NK cells in kidney transplant recipients, we investigated the peripheral NK cell repertoire, capacity to respond to various stimuli and impact of immunosuppressive drugs on NK cell activity in kidney transplant recipients. CD56(dim) NK cells of kidney transplanted patients displayed an activated phenotype characterized by significantly decreased surface expression of CD16 (p=0.0003), CD226 (p

In the context of kidney transplantation, little is known about the involvement of natural killer (NK) cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e., calcineurin-inhibitors like Cyclosporin A vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56(dim) NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on CD56(dim) NK cells was observed with significant differences between Cyclosporin A- and Tac-treated patients. Tac-treatment was associated with decreased CD69, HLA-DR, and increased CD94/NKG2A expression in CD56(dim) NK cells indicating that the quality of the immunosuppressive treatment impinges on the peripheral NK cell repertoire. In vitro studies with peripheral blood mononuclear cells of healthy donors showed that this modulation of CD16, CD6, CD69, and HLA-DR could also be induced experimentally. The presence of calcineurin or mTOR inhibitors had also functional consequences regarding degranulation and interferon-γ-production against K562 target cells, respectively. In summary, we postulate that the NK cell composition in peripheral blood of kidney transplanted patients represents an important hallmark of the efficacy of immunosuppression and may be even informative for the immune status after transplantation in terms of rejection vs. drug-induced allograft tolerance. Thus, NK cells can serve as sensors for immunosuppression and may be utilized for future strategies of an individualized adjustment of immunosuppression.

The lymphocyte surface glycoprotein CD26 anchors adenosine deaminase to the lymphocyte surface and possesses dipeptidyl peptidase IV activity. A distinct subset of CD26++ lymphocytes in autologous hematopoietic progenitor cell transplants (HPCTs) was investigated with regard to clinical outcome after autologous HPCT. The phenotype of these cells was characterized in more detail.Forty-two eligible patients (multiple myeloma, n = 31; Hodgkin's disease, n = 3; non-Hodgkin's lymphoma, n = 6; peripheral neuroectodermal tumor, n = 1; acute myeloid leukemia, n = 1) were included in a retrospective analysis. Distinct cellular subsets, including CD26+/- and CD26++ subpopulations, were analyzed for correlations with kinetics of engraftment, progression-free survival, and overall survival.The numbers of CD26++ T lymphocytes in the autograft correlated inversely with progression-free survival (p = 0.013). CD26++ T lymphocytes transfused per kg of body weight were predictive for the occurrence of disease progression or relapse (p = 0.006). Importantly, the numbers of CD26++ cells showed a highly variable degree of enrichment in the autograft, but no significant variations in the peripheral blood before apheresis. The characterization of CD26++ cells revealed that CD26++/CD8+ cells form a homogeneous population with a distinct T memory cell phenotype (CD45RO+, CD161++, interleukin-18Rα++, CCR7-).CD26++ lymphocytes define a discrete phenotype of T memory cells with known chemoresistance and T-cell-repopulating capacity. Their enrichment during apheresis and corresponding depletion from the circulation are associated with an adverse outcome in autologous HPCT.

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. Disclosures: No relevant conflicts of interest to declare.