Publications

Treatment of mice with mAb to L3T4 profoundly depletes T helper cells. This treatment inhibits humoral and cellular immunity, retards autoimmunity, and permits the induction of Ag-specific tolerance. Treatment of BALB/c mice with F(ab')2 anti-L3T4 inhibits humoral immunity without depleting L3T4+ cells, which is evidence that mAb to L3T4 may inhibit T helper cell function in vivo. In this report, we demonstrate that F(ab')2 anti-L3T4 also permits the induction of immune tolerance in a manner that is independent of T cell depletion. C57BL/6 mice were treated with 1 mg of F(ab')2 anti-L3T4 every other day for 18 days and from the onset were challenged weekly with the immunogen 2C7, a rat mAb to chicken ovalbumin. These mice failed to respond to 2C7 not only during the treatment period but also for at least 5 mo thereafter. This immune tolerance was Ag-specific; the mice rapidly produced antibodies to subsequent challenge with another Ag, human gamma-globulin. Unlike intact anti-L3T4, which immediately depletes L3T4+ cells by greater than 90%, F(ab')2 anti-L3T4 did not initially deplete cells and caused only a partial reduction by the end of the 18-day treatment. This partial reduction of L3T4+ cells did not contribute to the induction of tolerance because mice that were first challenged with 2C7 3 days after stopping the F(ab')2 anti-L3T4 treatment, when L3T4+ cells were lowest, had a normal Ir to 2C7. These findings demonstrate that mAb to L3T4 permits induction of Ag-specific immune tolerance by a mechanism independent of its ability to deplete L3T4+ cells. They also show that F(ab')2 anti-L3T4 treatment does not impair humoral immunity when immunization is initiated after treatment is stopped. Because L3T4 is homologous to CD4 in humans, our findings suggest that F(ab')2 anti-CD4 may offer significant advantages over the use of intact anti-CD4 as an immunosuppressive agent in humans.

We studied the roentgenograms, pulmonary function tests, and physical findings of 294 shipyard workers to evaluate asbestos exposure-cigarette smoking interactions. Roentgenographic parenchymal opacities, decreased pulmonary diffusing capacity for carbon monoxide, decreased flow at low lung volume, rales, and clubbing were each significantly related to the number of years elapsed since first exposure to asbestos and cigarette smoking status when analyzed by logistic regression. A dose-dependent cigarette smoking response that was consistent with synergism was present only for parenchymal opacities and decreased flow at low lung volume. These findings suggest that decreased flow at low lung volume, possibly reflecting peribronchiolar fibrosis, may be a functional corollary to smoking-associated parenchymal roentgenographic opacities among some asbestos-exposed individuals.