Abrogation of the requirement for feeder cell interaction and T cell receptor stimulation of lymphocytes infected with retroviral vectors.
Infection of sensitive adult mice with myeloproliferative sarcoma virus (MPSV) results in a myeloproliferative syndrome. Two components of the viral genome are required to induce this unique pathology: the mos oncogene and sequences within the U3 region of the long terminal repeat (LTR). In studies designed to identify the target cell of MPSV and thus better understand the mechanism by which a myeloproliferative syndrome is induced, we have infected a series of T cell lines with MPSV-based vectors. The results presented here show that infection with neoR MPSV abrogates the requirement for an antigen-specific or feeder cell-dependent stimulation, without altering the requirement for interleukin 2. Significantly, this response is not dependent on the mos oncogene, but requires sequences within the U3 region of the MPSV LTR. No alteration in the constitutive or induced levels of lymphokines released by these cells was observed. These results suggest a model in which T cells acquire a proliferative advantage by uncoupling the proliferative response from the lymphokine synthesis that is induced by activation of the T cell receptor. These cells are thus poised for antigen stimulation and secretion of cytokines that stimulate myelopoiesis.
Laker
C
C
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Federal Republic of Germany.
Gräning
G
G
Kelso
A
A
Stocking
C
C
Ostertag
W
W
D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D004261:DNA Replication; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis; D008980:Moloney murine sarcoma virus / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012091:Repetitive Sequences, Nucleic Acid; D009053:Sarcoma Viruses, Murine / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007376:Interleukin-2; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D016178:Granulocyte-Macrophage Colony-Stimulating Factor