USE OF ANTI-CD4(+) HYBRIDOMA CELLS TO INDUCE PNEUMOCYSTIS-CARINII IN MICE

A reduction in peripheral CD4(+) cell levels has been correlated with the onset of Pneumocystis canna pneumonia in AIDS patients, Most in vivo drug discovery and development for P. carinii have been conducted in corticosteroid-treated rats. There is need for the development of new small animal models with more selective methods of immunosuppression, This study outlines a new mouse model in which specific depletion of the CD4(+) T-lymphocyte population was achieved by subcutaneous injection of GK1.5 hybridoma cells into C3HeB/FeJ mice. A significant reduction in splenic CD4(+) cells was maintained over a 10-week period following a single injection of cells. Circulating anti-CD4(+) antibody wig detected throughout the 10-week period in hybridoma-injected mice, while circulating antibody was undetectable 4 weeks after repeated injection of purified monoclonal antibody. There was no significant increase in the CD8(+) cell populations of the hybridoma-injected mice. P. carinii cysts increased in the lungs of CD4(+) T-cell-depleted mice, with-the number of cysts detected comparable to levels in dexamethasone-treated mice. High levels of cysts were detected when CD4(+) cell populations in the spleen remained below 5% and decreased when CD4(+) populations increased above the 5% level. In mice, whose CD4(+) population was not reduced below 5%, there was no significant increase in P. carinii cysts detected. This study presents a new mouse model with specific immunosuppression requiring a minimum of animal manipulation for use in discovery and development of potential new therapeutics for P. carinii pneumonia.