Synergistic OX40 and CD30 signals sustain CD8+ T cells during antigenic challenge.
Prior to acquiring a memory phenotype, antigen-activated CD8(+) T cells need to expand and then undergo a contraction phase. Utilizing two different antigenic stimuli, we provide evidence that the tumor necrosis factor receptors OX40 and CD30 integrate synergistic signals during the expansion phase to help maintain CD8(+) effectors. Thus, double deficiency in OX40 and CD30 leads to CD8(+) cell loss during expansion after immunization either with OVA or with murine CMV. Following their contraction, OX40- and CD30-deficient CD8(+) T cells persist normally in CMV-infected mice. In contrast, persistence after OVA challenge is dependent on OX40 and CD30. Collectively, our data define the important role of both OX40 and CD30 during CD8(+) T-cell activation, and show that long-term CD8 persistence after contraction is regulated not only by stimulatory receptors but also by the nature of the antigen or how the antigen is presented.
Bekiaris
Vasileios
V
Medical Research Council Centre for Immune Regulation, Birmingham Medical School, University of Birmingham, Birmingham, UK. vbekiaris@liai.org
Gaspal
Fabrina
F
Kim
Mi-Yeon
MY
Withers
David R
DR
Sweet
Clive
C
Anderson
Graham
G
Lane
Peter J L
PJ
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D005434:Flow Cytometry; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D017730:Ki-1 Antigen / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053262:Receptors, OX40 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D000941:Antigens; D000956:Antigens, Viral; D017730:Ki-1 Antigen; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; D007371:Interferon-gamma