Cell-mediated immunity to the asexual blood stages of malarial parasites: animal models.
Studies using experimental models of malaria in immunodeficient mice and chickens have shown that resistance to blood-stage infection is mediated by protective antibodies and T cell-dependent cell-mediated mechanisms of immunity. Depending on the infecting species of Plasmodium and prior experience of the host, either humoral or cell-mediated immune mechanisms predominate. Cell-mediated immunity has been adoptively transferred with CD4+ splenic T cells, and with antigen-specific T cell lines and clones. Since ascending parasitemia occurs in all instances, the transferred cells do not kill plasmodia directly but appear to activate effector mechanisms capable of destroying the invading parasites. Both CD4+ and CD8+ T cells were found to increase in the spleens of malarious mice. Depletion of CD4+ T cells prevented nude mice adoptively transferred with immune splenic T cells from clearing parasitemia. In contrast, late treatment with anti-CD4 antibody had little if any effect. The converse was true when anti-CD8 antibody was utilized, i.e., a significant number of mice treated with anti-CD8 antibody after parasitemia became patent and had difficulty clearing blood parasites. These data suggest that during infection CD8+ T cells may become activated by CD4+ T cells responding to malarial antigens. These CD8+ T cells may be directly cytotoxic or secrete additional cytokines thereby amplifying the role of CD4+ T cells in the activation of anti-parasite effector mechanisms. Finally, a hypothesis is presented to explain how the parasite in natural infections may activate T cell-dependent effector mechanisms in order to control its numbers in host tissues thereby ensuring the survival of both parasite and host.
Weidanz
W P
WP
Malaria-Research Group, Department of Microbiology and Immunology, Philadelphia, PA 19102.
Melancon-Kaplan
J
J
Cavacini
L A
LA
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D002460:Cell Line; D002999:Clone Cells; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000469:parasitology; D007111:Immunity, Cellular / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D012008:Recurrence; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens