Publications

The maintenance of T lymphocytes which are important effectors of immune responses requires the T cell growth factor, interleukin 2 (IL-2). The binding of IL-2 to specific cell-surface receptors (IL-2R) has previously been shown to be essential to the growth and proliferation of activated lymphocytes. A human IL-2R cDNA sequence, placed under the control of the SV40 transcriptional promoter and enhancer, has been transfected into murine L cells. Single cell analysis by autoradiography was used to show that fibroblastic L cells, stably expressing human IL-2R, respond to stimulation with IL-2 by DNA synthesis and proliferation. This response is specifically blocked by the addition of an anti-IL-2R monoclonal antibody, anti-Tac, as previously reported. Neither nonspecific antisera nor 7G7/B6, an anti-IL-2R monoclonal antibody which does not interfere with IL-2 binding to its receptor, had any effect on this response. The induction of DNA synthesis by IL-2 is both rapid and dose-dependent. The ability of IL-2 to stimulate these transfected L cells to proliferate demonstrates that a lymphoid environment is not required for the functional interaction between IL-2 and its receptor, and provides a unique model system for the investigation of the molecular basis for the cellular events mediated by IL-2.

In this report, we have investigated the kinetics of IL-2 binding to the alpha (p55) and beta (p70) IL-2 binding proteins and compared these properties with ligand binding to the high-affinity IL-2-R. The association and dissociation of IL-2 to the alpha (p55) chain occurred with very rapid kinetics (t 1/2 = 4-10 s). In contrast, IL-2 association to, and dissociation from the beta (p70) chain occurred at a greatly reduced rate (t 1/2 = 40-50 min and 200-400 min, respectively). Measurements of IL-2 binding to the high-affinity receptor revealed an interesting composite of these binding properties with a rapid association rate (t 1/2 = 30-45 s) resembling the alpha (p55) chain and a slow dissociation rate (t 1/2 = 270-300 min) similar to the beta (p70) chain. These findings provide additional support for the model of the high-affinity IL-2-R as a heterodimeric membrane complex composed of both the alpha (p55) and beta (p70) subunits and suggest that high-affinity IL-2 binding may involve a conformational change in structure of either or possibly both of the receptor chains. These results highlight the important and perhaps different role played by each subunit in the formation of functional high-affinity IL-2-R.

The contribution of workplace exposures to the prevalence of asthma in adults has been minimized in the epidemiology of this illness. Analysis of the 1978 Social Security Disability Survey provides a population-based assessment as a novel approach utilizing self-attributed, occupationally related asthma as a measure of disease. Of 6,063 respondents, 468 (7.7 percent) identified asthma as a personal medical condition; 72 (1.2 percent [15.4 percent of all those with asthma]) attributed it to workplace exposures. These subjects were older and included more men and cigarette smokers than groups of both asthmatic and nonasthmatic subjects. The relative risk for occupationally attributed asthma was elevated among industrial and agricultural workers as compared with white collar and service occupations. Analysis of disability benefit status did not indicate that this introduced major reporting bias in this survey. This study suggests that occupational factors may have a greater role in adult asthma than previously thought.