Selectively impaired CD8+ but not CD4+ T cell cycle arrest during priming as a consequence of dendritic cell interaction with plasmodium-infected red cells.
Individuals living in malaria-endemic areas show generally low T cell responses to malaria Ags. In this study, we show murine dendritic cell (DC) interaction with parasitized erythrocytes (pRBC) arrested their maturation, resulting in impaired ability to stimulate naive, but not recall T cell responses in vitro and in vivo. Moreover, within the naive T cell population, pRBC-treated DC were selectively deficient in priming CD8(+) but not CD4(+) T cells. Indeed, DC that had taken up pRBC were shown for the first time to efficiently prime CD4(+) T cell responses to a known protective merozoite Ag, MSP4/5. In contrast, impaired priming resulted in decreases in both proliferation and cytokine production by CD8(+) T cells. Deficient priming was observed to both a model and a Plasmodium berghei-specific CD8(+) T cell epitope. The mechanisms underlying the inability of parasite-treated DC to prime CD8(+) T cells were explored. pRBC treatment of DC from wild-type C57BL/6, but not from IL-10 knockout animals, suppressed DC-mediated T cell priming across a Transwell, suggesting active IL-10-dependent suppression. CD8(+) T cells were arrested at the G(0) stage of the cell cycle after two cell divisions post-Ag stimulation. The proliferation arrest was partially reversible by the addition of IL-2 or IL-7 to responder cultures. These results suggest that in malaria-endemic areas, priming of CD8(+) T cell responses may be more difficult to induce via vaccination than the priming of CD4(+) T cells. Moreover, pathogens may selectively target the CD8(+) T cell arm of protective immunity for immune evasion.
Pouniotis
Dodie S
DS
Vaccine and Infectious Diseases Unit, The Austin Research Institute, Heidelberg, Victoria, Australia.
Proudfoot
Owen
O
Bogdanoska
Violeta
V
Scalzo
Karen
K
Kovacevic
Svetozar
S
Coppel
Ross L
RL
Plebanski
Magdalena
M
D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D002453:Cell Cycle; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D016753:Interleukin-10 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008288:Malaria / Q000097:blood / Q000276:immunology; D051379:Mice; D010961:Plasmodium / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
D007378:Interleukins; D016753:Interleukin-10