Generation and characterization of IL-2-activated veto cells.
The regulation of in vivo cytolytic response is important in a model of murine graft-vs-host disease induced by the injection of parental splenocytes into unirradiated B6D2F1 recipients. Injection of C57BL/6J spleen cells into B6D2F1 recipients results in an acute form of graft-vs-host disease that is characterized by the presence of CTL and suppressor cells, runting, and occasionally death. In contrast, injection of DBA/2J spleen cells into B6D2F1 recipients results in a chronic form of graft-vs-host disease that is characterized by the lack of in vivo CTL and hyperproduction of Ig and autoantibodies that results in an SLE-like syndrome. One reason for the lack of donor antirecipient CTL after injection of DBA/2J donor cells is that B6D2F1 recipient cells functionally inactivate the donor DBA/2J CTL precursor cells by expressing veto activity. These B6D2F1 veto cells are radiosensitive, inhibited by anti-CD8 antibodies, found primarily in lymph nodes, and were further characterized by testing the response of these inhibitory cells to lymphokines. These studies indicate that IL-2 can potentiate the activity of the veto cells induced in vivo and veto cells with a similar phenotype can be generated by in vitro incubation of naive lymph node cells with IL-2. These cells have been designated as IL-2-activated veto cells or LAV cells. IL-2 did not increase inhibitory activity by increasing the number of CD8+ cells or the number of CD8 molecules on the LAV cell surface but by altering the activation state of the LAV cell. The inhibitory capabilities of antibodies binding various cell surface molecules indicated that CD2 and intercellular adhesion molecule-1 molecules in addition to CD8 molecules played a role in the function of LAV cells.
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Department of Medicine, Rhode Island Hospital, Providence.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D016827:CD8 Antigens / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000517:prevention & control; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1