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Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells.

Publication ,  Journal Article
Yu, Y; Zitzner, JR; Houlihan, J; Herrera, N; Xu, L; Miller, J; Mathew, JM; Tambur, AR; Luo, X
Published in: PLoS One
2011

Human CD8(+) regulatory T cells, particularly the CD8(+)CD28(-) T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8(+) T cells which results in significant expansions of donor-specific CD8(+)CD28(-) T suppressor cells in vitro. The expanded CD8(+)CD28(-) T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4(+) T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8(+)CD28(-) T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation.

Duke Scholars

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

12

Start / End Page

e28948

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Tissue Donors
  • Species Specificity
  • Phenotype
  • Interleukin Receptor Common gamma Subunit
  • Interferon-gamma
  • Humans
  • Histocompatibility Testing
  • Histocompatibility Antigens Class II
  • Histocompatibility Antigens Class I
 

Citation

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Yu, Y., Zitzner, J. R., Houlihan, J., Herrera, N., Xu, L., Miller, J., … Luo, X. (2011). Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells. PLoS One, 6(12), e28948. https://doi.org/10.1371/journal.pone.0028948
Yu, Yuming, Jennifer R. Zitzner, Josetta Houlihan, Nancy Herrera, Luting Xu, Joshua Miller, James M. Mathew, Anat R. Tambur, and Xunrong Luo. “Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells.PLoS One 6, no. 12 (2011): e28948. https://doi.org/10.1371/journal.pone.0028948.
Yu Y, Zitzner JR, Houlihan J, Herrera N, Xu L, Miller J, et al. Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells. PLoS One. 2011;6(12):e28948.
Yu, Yuming, et al. “Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells.PLoS One, vol. 6, no. 12, 2011, p. e28948. Pubmed, doi:10.1371/journal.pone.0028948.
Yu Y, Zitzner JR, Houlihan J, Herrera N, Xu L, Miller J, Mathew JM, Tambur AR, Luo X. Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells. PLoS One. 2011;6(12):e28948.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

12

Start / End Page

e28948

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Tissue Donors
  • Species Specificity
  • Phenotype
  • Interleukin Receptor Common gamma Subunit
  • Interferon-gamma
  • Humans
  • Histocompatibility Testing
  • Histocompatibility Antigens Class II
  • Histocompatibility Antigens Class I