Effector CD8 T cells possess suppressor function after 4-1BB and Toll-like receptor triggering.
To better understand how innate and adaptive immune responses interact with each other, we combined 4-1BB T cell costimulation with specific adjuvants to determine whether these treatments would influence specific T cell expansion and function in vivo. In the presence of 4-1BB ligation and Toll-like receptor 3 (TLR)3 and/or TLR4 triggering, CD8 T cell clonal expansion and survival was augmented profoundly. Specific T cells primed in vivo with TLR ligands responded normally to in vitro recall stimulus, but, surprisingly, copriming with 4-1BB costimulation significantly impaired the recall response even though many more specific effector T cells were rescued in vivo. Here, we demonstrate that the rescued CD8 T cells suppressed CD4 T cell proliferation via a type beta transforming growth factor-dependent mechanism. Thus, 4-1BB and TLR ligands induce survival of specific effector CD8 T cells with suppressive recall potential, which may explain the dual role that 4-1BB activation plays in mediating tumor clearance and prevention of autoimmune disease.
Myers
Lara
L
Division of Immunology, University of Connecticut Health Center, Farmington, CT 06032, USA.
Takahashi
Chikara
C
Mittler
Robert S
RS
Rossi
Robert J
RJ
Vella
Anthony T
AT
D000818:Animals; D015703:Antigens, CD; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D029721:Drosophila Proteins; D005434:Flow Cytometry; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D011956:Receptors, Cell Surface / Q000276:immunology*; D017475:Receptors, Nerve Growth Factor / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9