Use of anti-CD4+ hybridoma cells to induce Pneumocystis carinii in mice.
A reduction of peripheral CD4+ cell levels has been correlated with the onset of Pneumocystis carinii 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 G.K1.5 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 was 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.
McFadden
D C
DC
Merck Research Laboratories, Rahway, New Jersey 07065-0900.
Powles
M A
MA
Smith
J G
JG
Flattery
A M
AM
Bartizal
K
K
Schmatz
D M
DM
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D006825:Hybridomas / Q000276:immunology; D016867:Immunocompromised Host; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis
D003907:Dexamethasone