Depletion of T-4+ lymphocytes with monoclonal antibody reactivates toxoplasmosis in the central nervous system: a model of superinfection in AIDS.
Central nervous system toxoplasmosis causes disability and death in up to 30% of patients with acquired immune deficiency syndrome (AIDS). The source of the toxoplasma infection in these patients and the specific immune deficit that allows for this virulent form of the infection are unknown. By using a mouse model of toxoplasmosis, we found that selective depletion of T-4+ lymphocytes (CD4+ T cells) produces overwhelming infection and death in both acute and chronic toxoplasmosis. However, the pattern of infection is remarkably different in chronically infected mice as compared with acutely infected mice when the mice are depleted of CD4+ T cells. During acute infection loss of the CD4+ T cell population leads to severe systemic infection with only mild disease in the brain. In chronically infected mice depleted of CD4+ T cells, death follows severe CNS damage due to toxoplasma infection with only minor systemic involvement. In chronically infected mice treated with anti-CD4 monoclonal antibody, reactivation of the toxoplasma infection occurs despite high titers of circulating antitoxoplasma antibody. In parallel with these results in mice, CNS toxoplasmosis in AIDS patients may be due to reactivation of infection acquired much earlier in life.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000953:Antigens, Protozoan / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001921:Brain / Q000473:pathology; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D009894:Opportunistic Infections / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000473:pathology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000953:Antigens, Protozoan; D000954:Antigens, Surface