Lack of Effector Cell Function and Altered Tetramer Binding of Tumor-Infiltrating Lymphocytes
| Autor: | Kathrin Brommer, Ulrike Blohm, Felicia M. Rosenthal, Evelyn Roth, Hanspeter Pircher, Tilman Dumrese |
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| Rok vydání: | 2002 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic Male Fibrosarcoma Immunology Receptors Antigen T-Cell Epitopes T-Lymphocyte Mice Transgenic Cell Separation Streptamer CD8-Positive T-Lymphocytes Biology Mice Viral Proteins Interleukin 21 Lymphocytes Tumor-Infiltrating Tumor Cells Cultured Animals Lymphocytic choriomeningitis virus Immunology and Allergy Cytotoxic T cell Lymphocyte Count IL-2 receptor Antigen-presenting cell Antigens Viral Cells Cultured Glycoproteins Antigen Presentation CD11b Antigen Lymphokine-activated killer cell ZAP70 Histocompatibility Antigens Class I Natural killer T cell Immunity Innate Peptide Fragments Cell biology Mice Inbred C57BL Female Cell Division Neoplasm Transplantation Protein Binding |
| Zdroj: | The Journal of Immunology. 169:5522-5530 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Tumor-specific CD8 T cell responses to MCA102 fibrosarcoma cells expressing the cytotoxic T cell epitope gp33 from lymphocytic choriomeningitis virus were studied. MCA102gp33 tumors grew progressively in C57BL/6 mice, despite induction of peripheral gp33-tetramer+ T cells that were capable of mediating antiviral protection, specific cell rejection, and concomitant tumor immunity. MCA102gp33 tumors were infiltrated with a high number (∼20%) of CD11b+CD11c− macrophage-phenotype cells that were able to cross-present the gp33 epitope to T cells. Tumor-infiltrating CD8 T cells exhibited a highly activated phenotype but lacked effector cell function. Strikingly, a significant portion of tumor-infiltrating lymphocytes expressed TCRs specific for gp33 but bound MHC tetramers only after cell purification and a 24-h resting period in vitro. The phenomenon of “tetramer-negative T cells” was not restricted to tumor-infiltrating lymphocytes from MCA102gp33 tumors, but was also observed when Ag-specific T cells derived from an environment with high Ag load were analyzed ex vivo. Thus, using a novel tumor model, allowing us to trace tumor-specific T cells at the single cell level in vivo, we demonstrate that the tumor microenvironment is able to alter the functional activity of T cells infiltrating the tumor mass. |
| Databáze: | OpenAIRE |
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