Suppressor cells in coccidioidomycosis

Abstract

Patients with coccidioidomycosis manifest a wide variety of severity of infection. Patients with unifocal and particularly multifocal dissemination manifest a defect in host defense mechanisms. This study focuses on the in vitro response to PHA as an indicator of immunoregulatory mechanisms. Study subjects are divided into four groups: Group I—17, patients with active disseminated coccidioidomycosis and lesions in multiple organs; Group II—15, patients with active disseminated coccidioidomycosis and a single lesion; Group III—16, patients with active coccidioidomycosis confined to the lungs; and Group IV—18, patients in whom coccidioidomycosis is inactive. The response to PHA was heterogeneous, even within groups. When cells were cultured in the presence of indomethacin or R020-5720, Group I cells demonstrated highly significant augmentation of the response to PHA ( P < 0.002), whereas cells from Groups II to IV were unaffected. When adherent cells were removed by passage through a nylon wool column, the effect of indomethacin could no longer be demonstrated. Direct measurement of prostaglandin production (PGE 2 and PGF 2α) and thromboxane suggest that there is no difference in the quantity of these compounds produced by unstimulated or PHA-stimulated cells by Group I versus Group IV cells ( P = 0.2-0.4). Indomethacin or R020-5720 markedly inhibit the production of these compounds. Studies of the effect of exogenous prostaglandin on PHA-stimulated cells suggest that Group I cells may be more inhibited by PGF 1α and PGF 2α compared to Group IV cells. The data demonstrate that PHA cultures of cells from Group I patients are suppressed. The suppressor cell can be removed by adherence to nylon wool and is inhibited by indomethacin or R020-5720.