Ž . International Immunopharmacology 1 2001 1307–1319 www.elsevier.comrlocaterintimp Activation-induced T cell apoptosis by monocytes from stem cell products q Kazuhiko Ino a , Ana G. Ageitos b , Rakesh K. Singh c , James E. Talmadge c, ) a Department of Obstetrics and Gynecology, Nagoya UniÕersity School of Medicine, 65 Surumai-cho, Showa-ku, Nagoya 466-8550 Japan b Oncology Department, Fundacion Jimenez Diaz, SerÕicio de Oncologia, AÕada Reyes Catolicos, 2, Madrid 28015 Spain c Department of Pathology and Microbiology, UniÕersity of Nebraska Medical Center, 987660 Nebraska Medical Center, Omaha, NE 68198-5600, USA Received 31 October 2000; received in revised form 15 February 2001; accepted 28 February 2001 Abstract Ž . Ž We recently found that mobilized peripheral blood stem cell PSC products from both cancer patients and normal . q donors contain high levels of CD14 monocytes, which can inhibit the proliferation of allogeneic and autologous T cells. q Ž We found in our studies that using CD14 monocytes from mobilized PSC products from normal and cancer patient . Ž . 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 Ž . Ž . both mobilization and apheresis. Both phytohemagglutinin PHA - and interleukin IL -2-induced proliferation of steady-state Ž . q peripheral blood mononuclear cells PBMC were markedly inhibited by co-culture with irradiated CD14 monocytes, Ž q . although inhibition was significantly greater with PHA than with IL-2 stimulation. IL-2 predominately CD56 NK cells or Ž . Ž . 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 q 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. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Monocytes; Peripheral tolerance; T cells; IL-2; Mitogenesis q This research was supported in part by grant aRO1-CA61593 from the National Institutes of Health. ) Corresponding author. Tel.: q 1-402-559-5639; fax: q 1-402-559-4990. Ž . E-mail address: jtalmadg@unmc.edu J.E. Talmadge . 1567-5769r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S1567-5769 01 00062-5