CD2-mediated autocrine growth of herpes virus saimiri-transformed human T lymphocytes.
Herpes virus saimiri (HVS) immortalizes T lymphocytes from a variety of primates and causes acute T cell lymphomas and leukemias in nonnatural primate hosts. Here we have analyzed the requirements for growth of three HVS-transformed human T cell lines. The cells expressed the phenotype of activated T cells: two were CD4+, and one was CD8+. All three cells responded to all allogeneic human cell lines tested with enhanced proliferation, production of interleukin 2 (IL-2), and increased expression of the IL-2 receptor. Binding of CD2 to its ligand CD58 was the critical event mediating stimulation because: (a) monoclonal antibodies (mAbs) to CD2 and to CD58, but not to a variety of other surface structures, blocked induced and spontaneous proliferation and IL-2 production; (b) only anti-CD2 mAbs were stimulatory if crosslinked; (c) a nonstimulatory cell was rendered stimulatory by CD58 transfection; and (d) the cells responded specifically to CD58 on sheep red blood cells. Growth of the cells required activation because cyclosporin A and FK506 blocked stimulator cell-induced IL-2 production and proliferation as well as the spontaneous growth of the lines. Antibodies to the IL-2 receptor reduced proliferation of the cells and blocked IL-2 utilization. Taken together, these results show that HVS-transformed T cells proliferate in response to CD2-mediated contact with stimulator cells or with each other in an IL-2-dependent fashion. They suggest that HVS transforms human T cells to an activation-dependent autocrine growth.
Mittrücker
H W
HW
First Department of Medicine, University of Mainz, Germany.
Müller-Fleckenstein
I
I
Fleckenstein
B
B
Fleischer
B
B
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D002455:Cell Division; D002472:Cell Transformation, Viral; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007376:Interleukin-2; D011971:Receptors, Immunologic