IL-15 prolongs the duration of CD8+ T cell-mediated immunity in mice infected with a vaccine strain of Toxoplasma gondii.
Immunization of mice with a vaccine (ts-4) strain of Toxoplasma gondii is known to induce complete protection against subsequent lethal infection. Ts-4-mediated protection has been reported to be primarily dependent on IFN-gamma-producing CD8+ T cells. However, duration of CD8+ T cell-mediated immunity in the ts-4-vaccinated animals is not known. In the present study, the kinetics of the CD8+ T cell response in mice immunized with the ts-4 strain of T. gondii was evaluated. Optimal CD8+ T cell immunity persisted at least 6 mo after vaccination, and mice at this time point continued to overcome lethal challenge with a more virulent strain. However, at 9 mo postimmunization, CD8+ T cell immunity was severely diminished and the mice succumbed to Toxoplasma challenge. Pretreatment of animals, vaccinated 9 mo earlier, with rIL-15 prevented the mortality induced by Toxoplasma challenge. The protective effect of IL-15 treatment was due to a rise in the frequency of Ag-specific CD8+ T cells. CD8+ T cells from IL-15-administered animals showed increased proliferation and IFN-gamma production in response to antigenic restimulation. These findings suggest that rIL-15 can reverse the decline in the long-term CD8+ T cell immune response in mice immunized with vaccine strain of T. gondii.
Khan
I A
IA
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA. Imtiaz.Khan@dartmouth.edu
Casciotti
L
L
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000008:administration & dosage / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010835:Phytohemagglutinins / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D019409:Interleukin-15; D010835:Phytohemagglutinins; D016052:Protozoan Vaccines; D007371:Interferon-gamma