Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells

Keli L. Hippen, Paul Harker-Murray, Stephen B. Porter, Sarah C. Merkel, Aryel Londer, Dawn K. Taylor, Megan Bina, Angela Panoskaltsis-Mortari, Pablo Rubinstein, Nico Van Rooijen, Tatiana N. Golovina, Megan M. Suhoski, Jeffrey S. Miller, John E. Wagner, Carl H. June, James L. Riley, Bruce R. Blazar

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)-coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor β (TGF-β) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1 BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xenogeneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1 BBL.

Original languageEnglish (US)
Pages (from-to)2847-2857
Number of pages11
JournalBlood
Volume112
Issue number7
DOIs
StatePublished - Oct 1 2008

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T-cells
Tumor Necrosis Factor Receptors
Antigen-Presenting Cells
Regulatory T-Lymphocytes
Fetal Blood
Blood
Costimulatory and Inhibitory T-Cell Receptors
Artificial Cells
Transforming Growth Factors
Graft vs Host Disease
Cell culture
Grafts
Cell Culture Techniques
Monoclonal Antibodies
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells. / Hippen, Keli L.; Harker-Murray, Paul; Porter, Stephen B.; Merkel, Sarah C.; Londer, Aryel; Taylor, Dawn K.; Bina, Megan; Panoskaltsis-Mortari, Angela; Rubinstein, Pablo; Van Rooijen, Nico; Golovina, Tatiana N.; Suhoski, Megan M.; Miller, Jeffrey S.; Wagner, John E.; June, Carl H.; Riley, James L.; Blazar, Bruce R.

In: Blood, Vol. 112, No. 7, 01.10.2008, p. 2847-2857.

Research output: Contribution to journalArticle

Hippen, KL, Harker-Murray, P, Porter, SB, Merkel, SC, Londer, A, Taylor, DK, Bina, M, Panoskaltsis-Mortari, A, Rubinstein, P, Van Rooijen, N, Golovina, TN, Suhoski, MM, Miller, JS, Wagner, JE, June, CH, Riley, JL & Blazar, BR 2008, 'Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells', Blood, vol. 112, no. 7, pp. 2847-2857. https://doi.org/10.1182/blood-2008-01-132951
Hippen, Keli L. ; Harker-Murray, Paul ; Porter, Stephen B. ; Merkel, Sarah C. ; Londer, Aryel ; Taylor, Dawn K. ; Bina, Megan ; Panoskaltsis-Mortari, Angela ; Rubinstein, Pablo ; Van Rooijen, Nico ; Golovina, Tatiana N. ; Suhoski, Megan M. ; Miller, Jeffrey S. ; Wagner, John E. ; June, Carl H. ; Riley, James L. ; Blazar, Bruce R. / Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells. In: Blood. 2008 ; Vol. 112, No. 7. pp. 2847-2857.
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AU - Porter, Stephen B.

AU - Merkel, Sarah C.

AU - Londer, Aryel

AU - Taylor, Dawn K.

AU - Bina, Megan

AU - Panoskaltsis-Mortari, Angela

AU - Rubinstein, Pablo

AU - Van Rooijen, Nico

AU - Golovina, Tatiana N.

AU - Suhoski, Megan M.

AU - Miller, Jeffrey S.

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