CD8(+) T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes


Chakravarty S., Cockburn I. A. , Kuk S., Overstreet M. G. , Sacci J. B. , Zavala F.

NATURE MEDICINE, cilt.13, ss.1035-1041, 2007 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 13 Konu: 9
  • Basım Tarihi: 2007
  • Doi Numarası: 10.1038/nm1628
  • Dergi Adı: NATURE MEDICINE
  • Sayfa Sayıları: ss.1035-1041

Özet

The success of immunization with irradiated sporozoites is unparalleled among the current vaccination approaches against malaria, but its mechanistic underpinnings have yet to be fully elucidated. Using a model mimicking natural infection by Plasmodium yoelii, we delineated early events governing the development of protective CD8(+) T-cell responses to the circumsporozoite protein. We demonstrate that dendritic cells in cutaneous lymph nodes prime the first cohort of CD8+ T cells after an infectious mosquito bite. Ablation of these lymphoid sites greatly impairs subsequent development of protective immunity. Activated CD8+ T cells then travel to systemic sites, including the liver, in a sphingosine-1-phosphate(S1P)-dependent fashion. These effector cells, however, no longer require bone marrow-derived antigen-presenting cells for protection; instead, they recognize antigen on parenchymal cells-presumably parasitized hepatocytes. Therefore, we report an unexpected dichotomy in the tissue restriction of host responses during the development and execution of protective immunity to Plasmodium.