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Ligation of the OX40 co-stimulatory receptor reverses self-Ag and tumor-induced CD8 T-cell anergy in vivo.
- Source :
-
European journal of immunology [Eur J Immunol] 2009 Aug; Vol. 39 (8), pp. 2184-94. - Publication Year :
- 2009
-
Abstract
- Tumor-specific CD8 T-cell peripheral tolerance occurs through clonal deletion, suppression, and the induction of anergy and can limit the generation of anti-tumor immunity. Several groups have demonstrated that prostate cancer can render tumor-specific CD8 T cells anergic, suggesting reversing tumor-induced anergy may greatly augment anti-tumor immunity. Recent work has demonstrated that signaling through the OX40 (CD134) co-stimulatory receptor, a member of the TNFR super-family, can augment CD4 and CD8 T-cell expansion, differentiation, and the generation of memory cells. However, whether OX40 ligation can reverse CD8 T-cell anergy, and more specifically, tumor-induced CD8 T-cell anergy, remains unclear. In the current study, we demonstrate that OX40 ligation can reverse CD8 T-cell anergy to a prostate-specific self-Ag in non-tumor-bearing hosts. Furthermore, OX40 engagement reversed tumor-specific CD8 T-cell anergy and restored the proliferative capacity of tumor-reactive CD8 T cells, which attenuated tumor growth and enhanced the survival of tumor-bearing hosts. These data demonstrate that OX40 ligation can rescue the function of anergic self- or tumor-reactive CD8 T cells in vivo and suggests that OX40-mediated therapy may provide a novel means of boosting anti-tumor immunity by restoring the responsiveness of previously anergic tumor-specific CD8 T cells.
- Subjects :
- Animals
Antigens, Neoplasm immunology
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes metabolism
Cell Differentiation immunology
Cell Line, Tumor
Clonal Anergy genetics
Cytotoxicity, Immunologic immunology
Flow Cytometry
Immunotherapy, Adoptive
Interleukin-2 Receptor alpha Subunit metabolism
Interleukin-7 Receptor alpha Subunit metabolism
L-Selectin metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Prostatic Neoplasms pathology
Prostatic Neoplasms therapy
Receptors, OX40 genetics
Signal Transduction immunology
T-Lymphocytes, Cytotoxic cytology
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic metabolism
CD8-Positive T-Lymphocytes immunology
Clonal Anergy immunology
Prostatic Neoplasms immunology
Receptors, OX40 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 39
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 19672905
- Full Text :
- https://doi.org/10.1002/eji.200939348