Regulation of the CD8+ T cell responses against Plasmodium liver stages in mice.
CD8+ T cells induced by immunization with Plasmodium sporozoites play a major role in protective immunity against parasite infection, inhibiting the development of liver stages. The activation of these T cells is initiated just a few hours after exposure to parasites and progresses rapidly through a tightly regulated program. Effector functions in CD8+ T are detectable as early as 24 h after immunization and this event is followed 24-48 h later by an accelerated expansion of the CD8+ T cell numbers which reaches a peak 4-5 days after priming. Concomitantly with the development of anti-parasite activity, CD8+ T cells acquire a self-regulatory role limiting the magnitude of the CD8+ T cell response. Once activated, CD8+ T cells strongly inhibit the priming of additional naive CD8+ T cells by competing for antigen presenting cells. On days 6-8 after immunization, a sudden contraction of this T cell response occurs due to programmed cell death of 70-80% of the activated cells. After this contraction phase, 15-20 days after priming, activated cells establish memory populations. The development and maintenance of these memory populations strictly depends on the presence of CD4+ T cells and IL-4, and probably also IL-7, IL-15 and IL-2. These cytokines, some of which are produced by CD4+ T cells, provide signals to prevents apoptosis and also induce the differentiation of memory sub-populations, most of which acquire definitive phenotypes 20-30 days after immunization.
Morrot
Alexandre
A
Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Zavala
Fidel
F
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular; D015847:Interleukin-4 / Q000276:immunology; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D010961:Plasmodium / Q000276:immunology*
D015847:Interleukin-4