The role of herpesvirus entry mediator as a negative regulator of T cell-mediated responses.
Herpesvirus entry mediator (HVEM), a TNF receptor superfamily member, has been previously described as a T cell costimulatory receptor. Surprisingly, HVEM-/- T cells showed enhanced responses to in vitro concanavalin A (ConA) stimulation when compared with WT T cells. Consistent with these findings, HVEM-/- mice exhibited increased morbidity and mortality as compared with WT mice in a model of ConA-mediated T cell-dependent autoimmune hepatitis. HVEM-/- mice produced higher levels of multiple cytokines, which were dependent on the presence of CD4+ T cells. Furthermore, HVEM-/- mice were more susceptible to MOG peptide-induced experimental autoimmune encephalopathy, and they showed increased T cell proliferation and cytokine production in response to antigen-specific challenge. Taken together, our data revealed an unexpected regulatory role of HVEM in T cell-mediated immune responses and autoimmune diseases.
Wang
Yang
Y
Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA.
Subudhi
Sumit K
SK
Anders
Robert A
RA
Lo
James
J
Sun
Yonglian
Y
Blink
Sarah
S
Wang
Yugang
Y
Wang
Jing
J
Liu
Xiaojuan
X
Mink
Karin
K
Degrandi
Daniel
D
Pfeffer
Klaus
K
Fu
Yang-Xin
YX
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; C506029:Tnfrsf14 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A