Expression of a tolerizing tumor antigen in peripheral tissue does not preclude recovery of high-affinity CD8+ T cells or CTL immunotherapy of tumors expressing the antigen
| Autor: | Aaron C. Shur, Claes Öhlén, Michael Kalos, Philip D. Greenberg, Doley J. Hong |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cytotoxicity
Immunologic medicine.medical_treatment Immunology Epitopes T-Lymphocyte Gene Products gag Mice Transgenic Biology CD8-Positive T-Lymphocytes Lymphocyte Activation Immunotherapy Adoptive Mice Antigen Antigens Neoplasm medicine Immune Tolerance Tumor Cells Cultured Immunology and Allergy Cytotoxic T cell Animals Cells Cultured Crosses Genetic Peripheral tolerance Immunotherapy medicine.disease Tumor antigen Friend murine leukemia virus Mice Inbred C57BL CTL Leukemia Tumor Virus Infections Liver Lymphocyte Transfusion Leukemia Erythroblastic Acute CD8 Retroviridae Infections T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 166(4) |
| ISSN: | 0022-1767 |
| Popis: | Transgenic (TG) mice were generated selectively expressing the gag protein of Friend murine leukemia virus (FMuLV) in the liver. FMuLVgag is also expressed by the FBL leukemia, and is the immunodominant tumor Ag of the CD8+ T cell response in C57BL/6 mice. gag-TG mice expressing FMuLVgag in the liver were tolerant to the protein and failed to generate a CTL response to either FBL or FMuLVgag. This tolerance reflected anergy rather than deletion, as CTL responsiveness could be recovered after four cycles of in vitro stimulation. Adoptively transferred gag-specific T cells were not anergized in gag-TG recipients, as revealed by antitumor activity in vivo. Also, such T cells did not induce detectable autoimmune injury in gag-TG liver cells. These results suggest that the requirements for a tissue Ag to provide a tolerizing stimulus are distinct from those for being the target of a T cell-mediated autoimmune response and that the requirements for induction and maintenance of peripheral tolerance are distinct for naive and primed T cells. That anergic T cells reactive with tumor-associated Ags can be recovered by repetitive in vitro stimulation and can mediate tumor therapy suggests strategies that use such Ags to generate CTL for adoptive immunotherapy should be further developed. |
| Databáze: | OpenAIRE |
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