Bystander activation of iNKT cells occurs during conventional T-cell alloresponses.

Journal article

It is well established that iNKT cells can be activated by both exogenous and a limited number of endogenous glycolipids. However, although iNKT cells have been implicated in the immune response to transplanted organs, the mechanisms by which iNKT cells are activated in this context remain unknown. Here we demonstrate that iNKT cells are not activated by allogeneic cells per se, but expand, both in vitro and in vivo, in the presence of a concomitant conventional T-cell response to alloantigen. This form of iNKT activation was found to occur independently of TCR-glycolipid/CD1d interactions but rather was a result of sequestration of IL-2 produced by conventional alloreactive T cells. These results show for the first time that IL-2, produced by activated conventional T cells, can activate iNKT cells independently of glycolipid/CD1d recognition. Therefore, we propose that the well-documented involvement of iNKT cells in autoimmunity, the control of cancer as well as following transplantation need not involve recognition of endogenous or exogenous glycolipids but alternatively may be a consequence of specific adaptive immune responses.

Authors: Jukes, J; Wood, K; Jones, N

• Publication status: Published
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• Volume: 12
• Issue: 3
• Pages: 590-599
• Publication date: 2012-03-01
• DOI: 10.1111/j.1600-6143.2011.03847.x
• EISSN: 1600-6143
• ISSN: 1600-6135
• Language: English
• Keywords: Natural Killer T-Cells; Isoantigens; Mice, Inbred C57BL; Mice, Transgenic; Cells, Cultured; T-Lymphocytes; Transplantation Tolerance; RNA, Messenger; Cell Proliferation; Interleukin-2; Blotting, Western; Mice, Inbred BALB C; Flow Cytometry; Mice; Graft Rejection; Real-Time Polymerase Chain Reaction; Graft Survival; Skin Transplantation; Cytokines; Lymphocyte Activation; Antigen Presentation; Female; Male; Enzyme-Linked Immunosorbent Assay; Animals; Antigens, CD1d; Apoptosis; Reverse Transcriptase Polymerase Chain Reaction; Bystander Effect