Lymphocyte changes during chronic administration of and withdrawal from corticosteroids: relation to Pneumocystis...

Corticosteroids were administered for up to 8 wk in adult Lewis rats to provoke Pneumocystis carinii pneumonia, and lymphocyte subsets were analyzed at different body sites with monoclonal antibodies by flow microfluorometry in a fluorescence activated cell sorter. The rats became chronically ill, debilitated, and exhibited marked involution of all lymphoid tissues. The lymphocytopenia was characterized in peripheral blood by a large fall in the frequency of T helper cells, and in the lungs by a fall in T helper (Th) cells and a rise in T suppressor (Ts) cells; at both sites there was reversal of the Th to Ts ratio. These changes were not found in the thymus, spleen, or bone marrow. When corticosteroids were withdrawn, the rats gained weight, cleared P. carinii from the lungs, and regenerated their lymphoid tissues. The lymphocyte subpopulations exhibited variation in their frequencies at different body sites, but gradually returned to baseline levels. Thus, in this model chronic corticosteroid administration results in profound generalized lymphocyte depletion and changes in the proportions of circulating and pulmonary T cell subsets. These abnormalities may be an important immunologic mechanism in the development of P. carinii pneumonia.