Perforin and Gamma Interferon Are Critical CD8+ T-Cell-Mediated Responses in Vaccine-Induced Immunity against Leishmania amazonensis Infection
AUTOR(ES)
Colmenares, María
FONTE
American Society for Microbiology
RESUMO
Previous studies have demonstrated that protection against New World leishmaniasis caused by Leishmania amazonensis can be elicited by immunization with the developmentally regulated Leishmania amastigote antigen, P-8. In this study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved. T-cell subset depletion experiments clearly indicate that elicitation of CD8+ (as well as CD4+) effector responses is required for protection. Further, mice lacking β2-microglobulin (and hence deficient in major histocompatibility complex class I antigen presentation) were not able to control a challenge infection after vaccination, indicating an essential protective role for CD8+ T effector responses. Analysis of the events ongoing at the cutaneous site of infection indicated a changing cellular dynamic involved in protection. Early postinfection in protectively vaccinated mice, a predominance of CD8+ T cells, secreting gamma interferon (IFN-γ) and expressing perforin, was observed at the site of infection; subsequently, activated CD4+ T cells producing IFN-γ were primarily found. As protection correlated with the ratio of total IFN-γ-producing cells (CD4+ and CD8+ T cells) to macrophages found at the site of infection, a role for IFN-γ was evident; in addition, vaccination of IFN-γ-deficient mice failed to provide protection. To further assess the effector mechanisms that mediate protection, mice deficient in perforin synthesis were examined. Perforin-deficient mice vaccinated with the P-8 antigen were unable to control infection. Thus, the elicitation of CD8+ T cell effector mechanisms (perforin, IFN-γ) are clearly required in the protective immune response against L. amazonensis infection in vaccinated mice.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=155724Documentos Relacionados
- A semiquantitative assay for CD8+ T-cell-mediated suppression of human immunodeficiency virus type 1 infection.
- Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria.
- Evidence for CD8+ T-cell immunity to murine rotavirus in the absence of perforin, fas, and gamma interferon.
- Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity
- Vaccination against persistent viral infection exacerbates CD4+ T-cell-mediated immunopathological disease.