Theophylline modulation of E-rosette formation: an indicator of T-cell maturation.

The binding of unsensitized sheep erythrocytes is a characteristic of human thymus dependent T-lymphocytes. We have investigated the effect of theophylline on E-rosette formation using cells from normal individuals, and patients with immunodeficiency or acute lymphoblastic leukaemia, and have attempted to correlate the influence of the drug on distinct T-lymphocyte subpopulations. Three subpopulations of E-rosetting T-lymphocytes can be delineated: theophylline-sensitive T-cells which lose the capacity to form E-rosettes following treatment; theophylline-resistant T-cells which are unaffected by the drug; and theophylline-dependent cells which acquire the ability to form E-rosettes following incubation with theophylline. The action of theophylline was shown to be dose-dependent, temperature-dependent and reversible. Reversibility or re-expression of the receptor for sheep red cells could be blocked by the addition of puromycin. In peripheral blood, E-rosetting T-lymphocytes were roughly divided into two equal populations, one sensitive, the other resistant. Thymocytes were shown to be entirely theophylline-resistant, whereas a small population of cells in peripheral blood and bone marrow were induced to become E-rosetting in the presence of theophylline. Induction by theophylline may be effective at a distinct stage of precursor T-cell differentiation.