Journal
JOURNAL OF IMMUNOLOGY
Volume 164, Issue 1, Pages 107-112Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.164.1.107
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI042858] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI42858A] Funding Source: Medline
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This report defines a cell surface receptor (OX40) expressed on effector CD4 T cells, which when engaged in conjunction with a danger signal, rescues Ag-stimulated effector cells from activation-induced cell death in vivo. Specifically, three signals were necessary to promote optimal generation of long-lived CD4 T cell memory in vivo: Ag, a danger signal (LPS), and OX40 engagement, Mice treated with Ag or superantigen (SAg) alone produced very few SAg-specific T cells. OX40 ligation or LPS stimulation, enhanced SAg-driven clonal expansion and the survival of responding T cells. However, when SAg was administered with a danger signal at the time of OX40 ligation, a synergistic effect was observed which led to a 60-fold increase in the number of long-lived, Ag-specific CD4 memory T cells. These data lay the foundation for the provision of increased numbers of memory T cells which should enhance the efficacy of vaccine strategies for infectious diseases, or cancer, while also providing a potential target (OX40) to limit the number of auto-Ag-specific memory T cells in autoimmune disease.
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