IL-15 induces alloreactive CD28- Memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation

O. Traitanon, A. Gorbachev, J. J. Bechtel, K. S. Keslar, W. M. Baldwin, E. D. Poggio, R. L. Fairchild

Research output: Contribution to journalArticle

Abstract

The presence of CD28- memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA-4Ig induction therapy. In vitro analyses have indicated poor alloantigen-induced CD28- memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28- memory CD8 T cell proliferation. Addition of IL-15, but not IL-2 or IL-7, to co-cultures of CD28- or CD28+ memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28- and enhanced CD28+ memory T cell proliferation. Proliferating CD28- memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28+ memory CD8 T cells. CTLA-4Ig inhibited alloantigen-induced proliferation of CD28+ memory CD8 T cell proliferation but had no effect on alloantigen plus IL-15-induced proliferation of either CD28- or CD28+ memory CD8 T cells. These results indicate the ability of IL-15, a cytokine produced by renal epithelial during inflammation, to provoke CD28- memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA-4Ig-mediated costimulation blockade. IL-15 induces the activation of alloreactive CD28 - memory CD8 T cells and confers resistance of alloreactive CD28 + memory CD8 T cells to CTLA-4Ig-mediated inhibition.

Original languageEnglish (US)
Pages (from-to)1277-1289
Number of pages13
JournalAmerican Journal of Transplantation
Volume14
Issue number6
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Interleukin-15
Cell Proliferation
T-Lymphocytes
Isoantigens
Kidney
Abatacept
Cytokines
Transplants
Interleukin-7
Graft Rejection
Coculture Techniques
Interferon-gamma
Interleukin-2

Keywords

  • belatacept
  • Costimulation
  • cytokines/cytokine receptors
  • immunosuppressant
  • T cell biology

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Traitanon, O., Gorbachev, A., Bechtel, J. J., Keslar, K. S., Baldwin, W. M., Poggio, E. D., & Fairchild, R. L. (2014). IL-15 induces alloreactive CD28- Memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation. American Journal of Transplantation, 14(6), 1277-1289. https://doi.org/10.1111/ajt.12719

IL-15 induces alloreactive CD28- Memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation. / Traitanon, O.; Gorbachev, A.; Bechtel, J. J.; Keslar, K. S.; Baldwin, W. M.; Poggio, E. D.; Fairchild, R. L.

In: American Journal of Transplantation, Vol. 14, No. 6, 2014, p. 1277-1289.

Research output: Contribution to journalArticle

Traitanon, O, Gorbachev, A, Bechtel, JJ, Keslar, KS, Baldwin, WM, Poggio, ED & Fairchild, RL 2014, 'IL-15 induces alloreactive CD28- Memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation', American Journal of Transplantation, vol. 14, no. 6, pp. 1277-1289. https://doi.org/10.1111/ajt.12719
Traitanon, O. ; Gorbachev, A. ; Bechtel, J. J. ; Keslar, K. S. ; Baldwin, W. M. ; Poggio, E. D. ; Fairchild, R. L. / IL-15 induces alloreactive CD28- Memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation. In: American Journal of Transplantation. 2014 ; Vol. 14, No. 6. pp. 1277-1289.
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abstract = "The presence of CD28- memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA-4Ig induction therapy. In vitro analyses have indicated poor alloantigen-induced CD28- memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28- memory CD8 T cell proliferation. Addition of IL-15, but not IL-2 or IL-7, to co-cultures of CD28- or CD28+ memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28- and enhanced CD28+ memory T cell proliferation. Proliferating CD28- memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28+ memory CD8 T cells. CTLA-4Ig inhibited alloantigen-induced proliferation of CD28+ memory CD8 T cell proliferation but had no effect on alloantigen plus IL-15-induced proliferation of either CD28- or CD28+ memory CD8 T cells. These results indicate the ability of IL-15, a cytokine produced by renal epithelial during inflammation, to provoke CD28- memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA-4Ig-mediated costimulation blockade. IL-15 induces the activation of alloreactive CD28 - memory CD8 T cells and confers resistance of alloreactive CD28 + memory CD8 T cells to CTLA-4Ig-mediated inhibition.",
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AU - Bechtel, J. J.

AU - Keslar, K. S.

AU - Baldwin, W. M.

AU - Poggio, E. D.

AU - Fairchild, R. L.

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N2 - The presence of CD28- memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA-4Ig induction therapy. In vitro analyses have indicated poor alloantigen-induced CD28- memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28- memory CD8 T cell proliferation. Addition of IL-15, but not IL-2 or IL-7, to co-cultures of CD28- or CD28+ memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28- and enhanced CD28+ memory T cell proliferation. Proliferating CD28- memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28+ memory CD8 T cells. CTLA-4Ig inhibited alloantigen-induced proliferation of CD28+ memory CD8 T cell proliferation but had no effect on alloantigen plus IL-15-induced proliferation of either CD28- or CD28+ memory CD8 T cells. These results indicate the ability of IL-15, a cytokine produced by renal epithelial during inflammation, to provoke CD28- memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA-4Ig-mediated costimulation blockade. IL-15 induces the activation of alloreactive CD28 - memory CD8 T cells and confers resistance of alloreactive CD28 + memory CD8 T cells to CTLA-4Ig-mediated inhibition.

AB - The presence of CD28- memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA-4Ig induction therapy. In vitro analyses have indicated poor alloantigen-induced CD28- memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28- memory CD8 T cell proliferation. Addition of IL-15, but not IL-2 or IL-7, to co-cultures of CD28- or CD28+ memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28- and enhanced CD28+ memory T cell proliferation. Proliferating CD28- memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28+ memory CD8 T cells. CTLA-4Ig inhibited alloantigen-induced proliferation of CD28+ memory CD8 T cell proliferation but had no effect on alloantigen plus IL-15-induced proliferation of either CD28- or CD28+ memory CD8 T cells. These results indicate the ability of IL-15, a cytokine produced by renal epithelial during inflammation, to provoke CD28- memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA-4Ig-mediated costimulation blockade. IL-15 induces the activation of alloreactive CD28 - memory CD8 T cells and confers resistance of alloreactive CD28 + memory CD8 T cells to CTLA-4Ig-mediated inhibition.

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