IL-4 receptor expression on CD8+ T cells is required for the development of protective memory responses against liver stages of malaria parasites.
IL-4 receptor (IL-4R)-deficient CD8+ T cells specific for the circumsporozoite protein of Plasmodium yoelii develop a severely impaired memory response after priming with parasites. Memory CD8+ T cells lacking the IL-4R are unable to establish a stable population residing in nonlymphoid organs, although they develop normally in lymphoid organs. Because memory cells from nonlymphoid organs disappear shortly after immunization, the protective antiparasitic activity of this T cell response also is lost. These results demonstrate that IL-4/IL-4R interactions on CD8+ T cells play a critical role in modulating the development and tissue distribution of memory cells induced by parasite immunization. They also indicate that memory cells residing in nonlymphoid tissues are critical for protective immunity against malaria parasites.
Morrot
Alexandre
A
Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Hafalla
Julius C R
JC
Cockburn
Ian A
IA
Carvalho
Luzia H
LH
Zavala
Fidel
F
D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D002454:Cell Differentiation / Q000276:immunology; D007111:Immunity, Cellular; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology*; D014611:Vaccination
D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019948:Receptors, Interleukin-4; C041595:circumsporozoite protein, Protozoan; D015847:Interleukin-4