Abstract:
Efforts to establish T lymphocytes in culture led to the discovery of T-cell growth factor (TCGF), its purification and characterization, and studies on the structure and function of its genetic locus. Application of this culture system to malignant T cells led to the identification of an exogenous retrovirus, human T-cell leukemia virus (HTLV), associated with a distinct form of clinical disease. TCGF receptors are universally present on HTLV-transformed cell lines despite the fact that many of these cell lines neither require nor produce TCGF. Characterization of TCGF and regulation of TCGF production are described. Soon after its discovery, TCGF was utilized for the growth of malignant T cells as well. This allowed the establishment of several cell lines from patients with cutaneous T-cell lymphomas. These cell lines recapitulated the morphology, cytochemical staining, and monoclonal antibody surface reactivity of the fresh tumor tissue. It was from one of these cell lines that a retrovirus was detected by the presence of particle-associated transverse transcriptase activity in the medium and the presence of c-type particles by electron microscopy. This virus has been called HTLV and has been extensively characterized. The presence of TCGF receptors on all HTLV-transformed cell lines, the existence of cell lines growing in the absence of added TCGF, and the finding of constitutive production of TCGF by some of the cell lines suggested that these malignant T cells may be producing and responding to their own TCGF, and driving their own proliferation. The failure to detect TCGF in the medium of all cell lines growing independently of exogenous TCGF did not exclude the possible involvement of low levels of extracellular TCGF or the presence of intracellular TCGF. However, the TCGF mRNA could not be detected in many of these TCGF-independent cell lines. Studies of oncogene expression in attempting to elucidate further the mechanism of cellular transformation have demonstrated the presence of c-sis transcripts in many HTLV-transformed cell lines, but no other hematopoietic cells examined. Characterization of the expressed c-sis sequences revealed that (1) they are capable of transforming 3T3 cells and (2) the sequence of the v-sis homologous region is identical to that of the normal gene. However, complete understanding of the role of sis expression in HTLV-induced transformation of T lymphocytes requires further investigation. (99 Refs)
Keywords: *Cell Transformation, Neoplastic *Cell Transformation, Viral Human HTLV-BLV Viruses Interleukin-2/GENETICS/*PHYSIOLOGY Oncogenes Platelet-Derived Growth Factor/*PHYSIOLOGY Proto-Oncogenes MEETING PAPER
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