Activation-induced T cell apoptosis by monocytes from stem cell products

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 autologo us T cells. We found in our studies that using CD14(+) monocytes from mobil ized PSC products (from normal and cancer patient donors), normal apheresis products or normal peripheral blood (PB) can affect lymphocyte function an d apoptosis-dependent T cell activation. However, it appears that the apopt osis is dependent on the frequency of monocytes, which is: increased by bot h mobilization and apheresis. Both phytohemagglutinin (PHA)- and interleuki n (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 wit h IL-2 stimulation. IL-2 (predominately CD56(+) NK cells) or anti-CD3 monoc lonal 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 wa s 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 reveal ed a significant increase in hypodiploid DNA, in a time-dependent manner, f ollowing co-culture of monocytes and PBMC in PHA, suggesting that T cell ap optosis occurred during PHA-induced activation, These results demonstrate t hat PSC-derived monocytes inhibit T cell proliferation by inducing the apop tosis of activated T cells and Nk: cells. but not steady-state cells. This suggests a potential role for monocytes in the induction of peripheral tole rance following stem cell transplantation, (C) 2001 Elsevier Science B,V. A ll rights reserved.