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Eur J Immunol. 2013 Jul;43(7):1839-48. doi: 10.1002/eji.201242842. Epub 2013 Jun 12.

4-1BB signal stimulates the activation, expansion, and effector functions of γδ T cells in mice and humans.

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  • 1Immune & Cell Therapy Branch, National Cancer Center, Ilsan, Gyeonggi-do, Korea.


We show here that the expression of 4-1BB is rapidly induced in γδ 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 γδ rather than αβ T cells protect mice from Listeria monocytogenes (LM) infection and 4-1BB stimulation enhances the γδ T-cell activities in the acute phase of LM infection. IFN-γ produced from γδ T cells was the major soluble factor regulating LM infection. Vγ1(+) T cells were expanded in LM-infected mice and 4-1BB signal triggered an exclusive expansion of Vγ1(+) T cells and induced IFN-γ in these Vγ1(+) T cells. Similarly, 4-1BB was induced on human γδ T cells and shown to be fully functional. Combination treatment with human γδ T cells and anti-hu4-1BB effectively protected against LM infection in human γδ T cell-transferred NOD-SCID mice. Taken together, these data provide evidence that the 4-1BB signal is an important regulator of γδ T cells and induces robust host defense against LM infection.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


4-1BB; IFN-γ; Listeria monocytogenes; γδ T cells

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