Growth of human normal and leukemic T cells: T-cell growth factor (TCGF) and the isolation of a new class of RNA tumor viruses (HTLV).

A system for routine long-term growth of human mature T-lymphocytes in liquid suspension culture was developed in our laboratory about 5 years ago. This system involves the continuous use of a factor, termed T-cell growth factor (TCGF) for the propagation of T-lymphocytes previously activated by lectin (PHA or Con A) or by antigen. Normal human T cells do not respond to TCGF unless they are first activated to become blast cells by antigen or lectin, presumably because they do not contain TCGF receptors until activated. We think then that TCGF is the physiological growth promoter in the immune response of T-lymphocytes, acting as the second signal (after antigen) in the immune response. These T cells show functional features, e.g., cytotoxic or helper function and other evidence of maturity. By using purified TCGF free of PHA and of lymphokines other than TCGF, we have recently been able to grow routinely neoplastic T cells from patients with leukemias and lymphomas of mature T cells, e.g., from patients with the Sezary syndrome and those with mycosis fungoides (cutaneous T-cell leukemias and lymphomas). Of considerable interest, the neoplastic T cells respond directly to TCGF; unlike normal T Cells they do not require prior in vitro activation with antigen or lectin. This indicates that transformed mature T cells already express TCGF receptors. This may be an important functional difference between normal and transformed human T cells. From some of these new cell lines we have recently isolated a new class of RNA tumor viruses (retroviruses), which we call HTLV. For several reasons we believe these are the first unambiguous isolates of RNA tumor viruses from humans. For instances, we now have data that these new viruses are easily distinguishable from all previously isolated viruses from animals. In addition, we have found antibodies in sera of some patients with these diseases specifically reactive with proteins of these viruses.