Depletion of L3T4+ (CD4+) T lymphocytes prevents development of resistance to Toxoplasma gondii in mice

Abstract

The role of L3T4+ (CD4+) T lymphocytes in the resistance of mice of different haplotypes to Toxoplasma gondii was examined, using the monoclonal antibody GK 1.5. Outbred Swiss-Webster or inbred CBA/Ca (H-2k), BALB/c (H-2d), and C57BL/6 (H-2b) mice injected with monoclonal antibody GK 1.5 24 h before and 24 h and 7, 15, and 21 days after oral inoculation with 10 live cysts of the low-virulence strain ME49 of T. gondii exhibited an almost complete abrogation of their antibody and cell-mediated immune responses to the parasite. Delayed-type hypersensitivity response and lymphocyte stimulation assays showed significantly reduced values compared with those of control mice inoculated with ME49 cysts but not treated with the monoclonal antibody. The number of T. gondii cysts in the brains of GK 1.5-treated mice was significantly higher than in controls. Challenge of the GK 1.5-treated and chronically infected mice with the virulent RH strain of T. gondii resulted in 100% mortality, whereas 100% of chronically infected controls survived the infection. These results suggest that L3T4+ (CD4+) T lymphocytes actively participate in the development of resistance to T. gondii and in the mechanisms controlling the formation of cysts of the parasite in the brains of mice.