Critical synergy of CD30 and OX40 signals in CD4 T cell homeostasis and Th1 immunity to Salmonella.
CD30 and OX40 (CD134) are members of the TNFR superfamily expressed on activated CD4 T cells, and mice deficient in both these molecules harbor a striking defect in the capacity to mount CD4 T cell-dependent memory Ab responses. This article shows that these mice also fail to control Salmonella infection because both CD30 and OX40 signals are required for the survival but not commitment of CD4 Th1 cells. These signals are also needed for the survival of CD4 T cells activated in a lymphopenic environment. Finally, Salmonella and lymphopenia are shown to act synergistically in selectively depleting CD4 T cells deficient in OX40 and CD30. Collectively these findings identify a novel mechanism by which Th1 responses are sustained.
Gaspal
Fabrina
F
Medical Research Council Centre for Immune Regulation, Division of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom.
Bekiaris
Vasileios
V
Kim
Mi-Yeon
MY
Withers
David R
DR
Bobat
Saeeda
S
MacLennan
Ian C M
IC
Anderson
Graham
G
Lane
Peter J
PJ
Cunningham
Adam F
AF
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000235:genetics; D017730:Ki-1 Antigen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008211:Lymphocyte Cooperation / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D053262:Receptors, OX40 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
D017730:Ki-1 Antigen; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse