Several isolates of human T-cell leukemia/lymphoma virus (HTLV) were transmitted to normal human T cells obtained from the umbilical cord blood of newborns. T cells from seven specimens were immortalized by infection with different HTLV isolates and their properties were compared with those of' activated uninfected normal T cells grown in the presence of Tcell growth factor (TCGF) and with those of HTLV-positive neoplastic T-cell lines derived from patients with T-cell malignancies. The HTLV-infected cells generally belonged to a class of mature T cells (OKT4' and Leu 3A+) and differed from the normal uninfected cells in that they could be propagated in culture indefinitely; possessed altered morphology, including convoluted nuclei and some bi-and multinucleated giant cells; formed large clumps in culture; demonstrated' a diminished requirement for TCGF; had an increased density of TCGF receptors; often became completely independent of exogenous TCGF; and expressed HLA-DR determinants. These properties of the HTLV-infected cord blood T cells contrasted to those of uncultured cord blood T cells and of cord blood cells stimulated with mitogen-and grown with TCGF but resembled the characteristics of T-cell lines established previously from patients with HTLV-associated T-cell malignancies. This in vitro system offers a-unique opportunity to study the basic mechanism involved in abnormal growth and neoplastic transformation of a specific class of human T cells.The discovery of T-cell growth factor (TCGF) in 1976 (1) enabled the development of the-technology to grow normal and neoplastic mature T cells in vitro for considerable periods of time (2). Using purified TCGF (3), it was possible to grow in culture T cells that exhibited several characteristics of the primary tumor cells from patients with mature T-cell malignancies (2). A type C retrovirus designated human T-cell leukemia/ lymphoma virus (HTLV) was isolated from,some neoplastic Tcell lines (4-7). Detailed characterization of these isolates showed that HTLV is an exogenous human retrovirus closely linked to a subtype of mature T-cell malignancy and distinct from all-known animal retroviruses (8-15). In our laboratory 15 HTLV isolates have been obtained from people of different parts of the world (4-7). In addition, human retrovirus isolates have been inde-., pendently reported by workers in other laboratories (16)(17)(18) and comparative studies have shown that the new isolates are members of the HTLV group (19).HTLV infection of normal T cells can induce long-term growth of the infected cells (16,20). One source of HTLV, the MT-2 cell line, was derived from umbilical cord blood T cells designed to -be a "feeder cell" for growing leukemia T cells in a cocultivation experiment, but the cord blood T cells incidentally became immortalized by an apparent infection with HTLV derived from the leukemia cells (16). Yamamoto et al. (21) recently confirmed this observation by using a MT-2 isolate for infection of human lymphocytes. We have transmitted numerou...

Fifty of 75 serum samples collected in the West Nile district of Uganda between August 1972 and July 1973 contained antibodies reactive with human T-cell leukemia (lymphotropic) virus type 3 (HTLV-III; mean titer, 601), while 12 of 75 samples were positive in a similar test for HTLV type 1 (HTLV-1) antibodies (mean titer, 236). The samples were screened by enzyme-linked immunosorbent assay and positive results were confirmed by a newly developed unlabeled antibody-peroxidase procedure with enhanced sensitivity for detection of antibody binding to immunoblots of HTLV-III antigen, demonstrating antibodies to proteins with molecular weights of 24,000, 41,000, and 76,000 in nearly all positive samples. Analysis of titration data indicated enhanced titers of antibody against HTLV-III and HTLV-I when coinfection occurred. The high prevalence and relatively low titers [compared to serum from patients with acquired immune deficiency syndrome (AIDS)] of antibodies recognizing HTLV-III proteins in sera from this population at a time that may predate or coincide with the appearance or spread of the AIDS agent (HTLV-III) suggest that the virus detected may have been a predecessor of HTLV-III or is HTLV-III itself but existing in a population acclimated to its presence. It further suggests an African origin of HTLV-III.

The effect of UV-B irradiation on the expression of membrane-associated IL 1 (mIL 1) by rat pulmonary alveolar macrophages (PAM) was studied. We found that although there was an increase in secreted IL 1 by PAM exposed to UV-B, the expression of mIL 1 was inhibited in a dose-dependent manner. Furthermore, PAM that were allowed to express mIL 1 before UV-B irradiation had a faster decay of mIL 1 activity than unirradiated cells. These data suggested that mIL 1 expression is inhibited by UV-B irradiation, and that under normal circumstances, mIL 1 synthesis and degradation is at a steady state, with the half-life of mIL 1 activity being 24 hr when assayed in an IL 1-dependent cell line proliferation assay. These data indicate that secreted forms of IL 1 and mIL 1 are differentially regulated and that the therapeutic effects of UV irradiation may be due to its inhibition of mIL 1 activity.