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

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.

• Authors: O Traitanon, A Gorbachev, J J Bechtel, K S Keslar, W M Baldwin 3rd, E D Poggio, R L Fairchild
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 14 Issue 6 Pg. 1277-89 (Jun 2014) ISSN: 1600-6143 [Electronic] United States
• PMID: 24842641 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• CD28 Antigens
• CTLA-4 Antigen
• Interleukin-15

Topics

• CD28 Antigens (immunology)
• CD8-Positive T-Lymphocytes (cytology, immunology)
• CTLA-4 Antigen (immunology)
• Humans
• Immunologic Memory
• Interleukin-15 (physiology)
• Lymphocyte Activation
• Lymphocyte Culture Test, Mixed