Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After immunization of B6 mice with the syngeneic retrovirus-induced T cell leukemia/lymphoma FBL-3, two major tumor-specific proliferative T cell clonotypes were derived. T cell clones derived from long-term lines propagated by in vitro culture with irradiated tumor cells and syngeneic spleen cells were exclusively of the Lyt-2+ phenotype. Such clones were cytolytic, retained their proliferative phenotype indefinitely when expanded by repeated cycles of reactivation and rest, and recognized a tumor-specific cell surface antigen in association with class I MHC molecules. This tumor cell antigen was not present on nontransformed virus-infected cells. Class II MHC-restricted MT4+ clones specific for the viral antigen gp70 were derived from lymph node T cells of FBL-3 tumor-immune mice only by in vitro culture with purified Friend virus in the presence of syngeneic splenic APC. Once derived, however, such clones could be stimulated in the presence of FBL-3 tumor cells and syngeneic spleen cells, demonstrating the reprocessing of tumor-derived gp70 antigen by APC in the spleen cell population. In contrast, no reprocessing of the tumor cell surface antigen by splenic APC for presentation to the class I MHC-restricted T cell clones could be demonstrated. Evidence is presented that FBL-3 T leukemia/lymphoma cells function as APC for Lyt-2+ class I MHC-restricted clones, and that no concomitant recognition of Ia molecules is required to activate these clones. Both Lyt-2+ and MT4+ clones were induced to proliferate in the presence of exogenous IL2 alone, but this stimulus failed to result in significant release of immune interferon. In contrast, antigen stimulation of both clones resulted in proliferation as well as significant immune interferon release. Immune interferon production is not required for the generation of MHC-restricted cell-mediated cytolytic function.
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PMID:Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor-specific cell surface antigen. 258 53

The aim of our study was to examine the potential usefulness of transducing the protein kinase C-gamma (PKC-gamma) cDNA gene into tumor-specific T cells as a technique for facilitating the generation of large numbers of functional Ag-specific T for tumor therapy. Murine CD8+, F-MuLV gag-specific CTL clones, and CD4+, F-MuLV env-specific Th clones, as well as bulk-cultured T cell lines with defined Ag specificity to FBL-3, a Friend murine leukemia virus (F-MuLV)-induced tumor, were transduced with a retroviral vector pZipNeoPKC-gamma and selected in G418. The results demonstrated that PKC-gamma-transduced clones remained activated in culture, as evidenced by continued expression of up-regulated levels of IL-2R, which were as high after 6 mo in culture without Ag restimulation as 24 h after Ag stimulation. In vitro functional studies demonstrated that PKC-gamma-transduced CD8+ T cell clones maintained specific cytolytic activity to FBL-3, and PKC-gamma-transduced CD4+ T cell clones maintained specific proliferative activity to FBL-3 or F-MuLV Ag presented by irradiated syngeneic APC. Short-term bulk-cultured T cells specific to FBL-3 were also transduced and could be grown long term in vitro with maintenance of functional specificity. In vivo study showed that PKC-gamma-transduced CD4+ T cells were able to proliferate in response to Ag plus IL-2 stimulation in vivo in a similar pattern as the parental T cells. Therapy with adoptively transferred PKC-gamma-transduced T cell clones and lines into syngeneic mice, with or without FBL-3 tumor, showed that the PKC-gamma-transduced T cells were not tumorigenic and were effective in curing mice with disseminated FBL-3.
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PMID:Retroviral transduction of protein kinase C-gamma into tumor-specific T cells allows antigen-independent long-term growth in IL-2 with retention of functional specificity in vitro and ability to mediate tumor therapy in vivo. 793 May 83