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

Kazuhiko Ino, Ana G. Ageitos, Rakesh K Singh, James E Talmadge

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1307-1319
Number of pages13
JournalInternational Immunopharmacology
Volume1
Issue number7
DOIs
StatePublished - Jun 21 2001

Fingerprint

Monocytes
Stem Cells
Apoptosis
T-Lymphocytes
Interleukin-2
Phytohemagglutinins
Lymphocytes
Coculture Techniques
Blood Component Removal
Natural Killer Cells
Blood Cells
Cell Proliferation
Tissue Donors
Peripheral Tolerance
Stem Cell Transplantation
Neoplasms
Cell Cycle
Flow Cytometry
Monoclonal Antibodies
Peripheral Blood Stem Cells

Keywords

  • IL-2
  • Mitogenesis
  • Monocytes
  • Peripheral tolerance
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Activation-induced T cell apoptosis by monocytes from stem cell products. / Ino, Kazuhiko; Ageitos, Ana G.; Singh, Rakesh K; Talmadge, James E.

In: International Immunopharmacology, Vol. 1, No. 7, 21.06.2001, p. 1307-1319.

Research output: Contribution to journalArticle

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