title: 4-1BB signal stimulates the activation, expansion, and effector functions of γδ T cells in mice and humans.
abstract: 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.
authors: Immune & Cell Therapy Branch, National Cancer Center, Ilsan, Gyeonggi-do, Korea.
authors: Seung J
authors: SJ
authors: Lee
authors: Young H
authors: YH
authors: Kim
authors: Sun H
authors: SH
authors: Hwang
authors: Yu I
authors: YI
authors: Kim
authors: In S
authors: IS
authors: Han
authors: Dass S
authors: DS
authors: Vinay
authors: Byoung S
authors: BS
authors: Kwon
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002469:Cell Separation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: 4-1BB; IFN-γ; Listeria monocytogenes; γδ T cells