4-1BB signal stimulates the activation, expansion, and effector functions of [gamma][delta] T cells in mice and humans

• Published in: European journal of immunology Vol. 43; no. 7; p. 1839
• Main Authors: Lee, Seung J, Kim, Young H, Hwang, Sun H, Kim, Yu. I, Han, In S, Vinay, Dass S, Kwon, Byoung S
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.07.2013
• Subjects: Cell division; Expansion; Immunology; Infections; Lymphocytes
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242842

We show here that the expression of 4-1BB is rapidly induced in [gamma][delta] T cells following antigenic stimulation in both mice and humans, and ligation of the newly acquired 4-1BB with an agonistic anti-4-1BB augments cell division and cytokine production. We further demonstrate that [gamma][delta] rather than [alpha][beta] T cells protect mice from Listeria monocytogenes (LM) infection and 4-1BB stimulation enhances the [gamma][delta] T-cell activities in the acute phase of LM infection. IFN-[gamma] produced from [gamma][delta] T cells was the major soluble factor regulating LM infection. V[gamma]1+ T cells were expanded in LM-infected mice and 4-1BB signal triggered an exclusive expansion of V[gamma]1+ T cells and induced IFN-[gamma] in these V[gamma]1+ T cells. Similarly, 4-1BB was induced on human [gamma][delta] T cells and shown to be fully functional. Combination treatment with human [gamma][delta] T cells and anti-hu4-1BB effectively protected against LM infection in human [gamma][delta] T cell-transferred NOD-SCID mice. Taken together, these data provide evidence that the 4-1BB signal is an important regulator of [gamma][delta] T cells and induces robust host defense against LM infection. [PUBLICATION ABSTRACT]