title: Activation-induced T cell apoptosis by monocytes from stem cell products.
abstract: We recently found that mobilized peripheral blood stem cell (PSC) products (from both cancer patients and normal donors) contain high levels of CD14+ monocytes, which can inhibit the proliferation of allogeneic and autologous T cells. We found in our studies that using CD14+ monocytes from mobilized PSC products (from normal and cancer patient donors), normal apheresis products or normal peripheral blood (PB) can affect lymphocyte function and apoptosis-dependent T cell activation. However, it appears that the apoptosis is dependent on the frequency of monocytes, which is increased by both mobilization and apheresis. Both phytohemagglutinin (PHA)- and interleukin (IL)-2-induced proliferation of steady-state peripheral blood mononuclear cells (PBMC) were markedly inhibited by co-culture with irradiated CD14+ monocytes, although inhibition was significantly greater with PHA than with IL-2 stimulation. IL-2 (predominately CD56+ NK cells) or anti-CD3 monoclonal antibody (mAb) and IL-2-expanded lymphocytes (activated T cells) were inhibited by PSC monocytes to a significantly greater level as compared to steady-state lymphocytes. Indeed, no inhibition of T cell proliferation was observed when lymphocytes were co-cultured in the absence of mitogenic or IL-2 stimulation. In contrast, an increased proliferation was observed in co-cultures of CD14+ monocytes and steady-state or activated lymphocytes without mitogenic stimulation. Cell cycle analysis by flow cytometry revealed a significant increase in hypodiploid DNA, in a time-dependent manner, following co-culture of monocytes and PBMC in PHA, suggesting that T cell apoptosis occurred during PHA-induced activation. These results demonstrate that PSC-derived monocytes inhibit T cell proliferation by inducing the apoptosis of activated T cells and NK cells, but not steady-state cells. This suggests a potential role for monocytes in the induction of peripheral tolerance following stem cell transplantation.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Surumai-cho, Showa-ku, Nagoya 466-8550 Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ino
authors.forename: A G
authors.initials: AG
authors.lastname: Ageitos
authors.forename: R K
authors.initials: RK
authors.lastname: Singh
authors.forename: J E
authors.initials: JE
authors.lastname: Talmadge
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D010835:Phytohemagglutinins