Publications

Radiolabeled molecules from detergent-solubilized human T cell blasts were fractionated on affinity supports coupled with T cell growth factor (TCGF) and anti-Tac antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that a glycoprotein of approximately 58,000 mol wt was bound in both cases. Sequential binding to the two affinity supports demonstrated that the molecules recognized in each instance were identical. Thus, the Tac antigen contains the cellular binding site for TCGF. Note added in proof: Preliminary binding experiments using high concentrations of [3H]leucine, lysine TCGF with a low specific radioactivity indicate the existence of a sizeable pool of receptor sites with an affinity 2,000-10,000 times lower than that of the high affinity receptors measured in Fig. 1. Such sites may explain the numerical discrepancy between early TCGF binding experiments (5) and the binding of the anti-Tac antibody. The hypothesis that the anti-Tac antibody apparently reacts with both classes of receptor would explain its effect on the physiological response (high affinity binding) and the high level of Tac antigen on the cell surface.

Certain adult T-cell lymphoproliferative disorders are associated with human T-cell leukaemia virus (HTLV), a unique human type C retrovirus. (The strains of HTLV used in these studies belong to the subgroup HTLV-I.) HTLV is not an endogenous agent in man, but rather is an acquired virus with T-cell tropism. Neoplastic cells from patients infected with HTLV generally express receptors for T-cell growth factor (TCGF) (interleukin-2), and do not require prior activation with antigens or lectins to undergo TCGF-induced proliferation. Furthermore, neoplastic T-cell lines originating from such patients may constitutively produce TCGF, TCGF receptors and HTLV virions. HTLV is transmissible from cell to cell, and the infection of human T cells in vitro is associated with the expression of TCGF receptors, which can be identified by the monoclonal antibody termed anti-Tac. In our experience to date, T-cell populations that produce HTLV without exception also express epitopes found on TCGF receptors. Recognition of an association between HTLV virions and the Tac antigen would have clinical and theoretical implications. We now present evidence that during the replication or release of HTLV, the virion becomes preferentially associated with the Tac antigen.

Nine asthmatic subjects exercised at low, moderate, and high work rates on a cycle ergometer while breathing filtered, humidified air with or without 0.5 ppm of sulfur dioxide (SO2) in a double-blind study. Subjects first performed these experiments breathing through a mouthpiece while wearing a noseclip (oral breathing) and then repeated the experiments breathing through a facemask that separated and permitted independent measurement of oral and nasal air flow (oronasal breathing). We determined specific airway resistance before and after exercise by body plethysmography. Inhaled by mouthpiece, 0.5 ppm So2 caused bronchoconstriction at moderate and high but not at low work rates. There was a dose-response relationship between the work rate performed and the degree of bronchoconstriction induced. Inhaled oronasally, 0.5 ppm SO2 caused bronchoconstriction only at the high work rate. These findings demonstrate that So2-induced bronchoconstriction is dependent on the work rate of exercise during exposure, that oronasal breathing is only partially effective in preventing the bronchoconstriction observed with oral breathing, and that oronasal breathing is less effective in preventing bronchoconstriction with high than with moderate exercise at this concentration of SO2.

To determine antihistaminic versus anticholinergic effects of atropine in airway smooth muscle, we used an in vitro preparation of canine trachealis muscle strips and determined atropine's effect on contractile responses induced by histamine or by electrical field stimulation of cholinergic nerves. In the first series of experiments, 53 strips had initial responses to field stimulation determined and were then randomly assigned to a control group or to a group treated with atropine before field stimulation was repeated and histamine was given. Atropine in concentrations of 10(-8), 10(-7), and 10(-6) M decreased the response to field stimulation to 61.4, 10.5, and 0% of the initial response, respectively, but had no effect on the responses to histamine. In the second series of experiments, 24 strips were treated with indomethacin to prevent histamine tachyphylaxis; these strips had initial responses to both field stimulation and histamine determined and were then assigned to a control group or to a group treated with atropine before field stimulation and histamine were repeated. In these experiments, a concentration of atropine (10(-6) M), which again completely blocked the response to field stimulation, still had no effect on histamine-induced contraction. We conclude that atropine in a concentration that completely blocks the response to cholinergic nerve stimulation has no antihistaminic effect.