A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes.

Abstract

Pulmonary infections with Pneumocystis carinfi are an impor- tant cause of morbidity and mortality in patients with AIDS. P. carinii infections are seen in patients with decreased numbers of helper T lymphocytes, suggesting that these cells are im- portant in preventing infection. To test this hypothesis, we sought to establish experimental infection with P. carinfi in mice selectively depleted of helper T lymphocytes. Weekly injections of a monoclonal anti-CD4 antibody produced sus- tained depletion of helper T lymphocytes from blood and lym- phoid organs. To establish pulmonary infection, lymphocytedepleted mice were then given intratracheal inoculations of P. carinji organisms derived from the lungs of chronically in- fected athymic mice. Pulmonary infection with P. carinli was demonstrable in the antibody-treated mice and was centered around the conducting airways. Infection was persistent for up to 3 mo with continued antibody treatments, and yet could be cleared from the lungs if antibody treatments were discontin- ued. This experimental model of P. carinji infection permits the study of infection associated with a specific immune defect and implicates the helper T lymphocyte as a critical cell in host defense against this pathogen. (J. Clin. Invest. 1990Invest. . 85:1686Invest. -1693.) .) pneumonia * Pneumocystis carinji immuno- suppression Introduction Pneumocystis carinii is an important cause of pneumonia in immunocompromised patients (1), particularly those with AIDS (2). Although P. carinii pneumonia can be treated with trimethoprim-sulfamethoxazole or pentamidine, fatality rates with initial infection range from 15 to 60% (3, 4). Improve- ment in the therapy of P. carinii pneumonia may require a better understanding of the pathogenesis of infection and how immunosuppression permits infection.