TY - JOUR
T1 - Myeloid Differentiation Factor 88 Is Required for Cross-Priming in Vivo
AU - Palliser, Deborah
AU - Ploegh, Hidde
AU - Boes, Marianne
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/3/15
Y1 - 2004/3/15
N2 - We describe a role for myeloid differentiation factor 88 (MyD88) in the induction of functional CTLs in vivo, in response to exogenously administered Ag, using a heat shock fusion protein, hsp65-P1, as a model Ag. CD8 T cells transferred into MyD88-deficient animals produce normal numbers of CD8 effector cells that have normal activation marker profiles after immunization with hsp65-P1. However, these CD8 T cells produced significantly less IFN-γ and showed reduced killing activity. This reduction .in activation of functional CTLs appears to be unrelated to Toll-like receptor 4 function, because in vitro hsp65-P1-experienced Toll-like receptor 4-deficient dendritic cells (DCs), but not MyD88-deficient DCs, activated CD8 T cells to a similar extent to wild-type DCs. We identify a cross-presentation defect in MyD88-deficient DCs that, when treated with hsp65-P1 fusion protein, results in surface display of fewer SIYRYYGL/class I MHC complexes. Thus, MyD88 plays a role in the developmental maturation of DCs that allows them to prime CD8 T cells through cross-presentation.
AB - We describe a role for myeloid differentiation factor 88 (MyD88) in the induction of functional CTLs in vivo, in response to exogenously administered Ag, using a heat shock fusion protein, hsp65-P1, as a model Ag. CD8 T cells transferred into MyD88-deficient animals produce normal numbers of CD8 effector cells that have normal activation marker profiles after immunization with hsp65-P1. However, these CD8 T cells produced significantly less IFN-γ and showed reduced killing activity. This reduction .in activation of functional CTLs appears to be unrelated to Toll-like receptor 4 function, because in vitro hsp65-P1-experienced Toll-like receptor 4-deficient dendritic cells (DCs), but not MyD88-deficient DCs, activated CD8 T cells to a similar extent to wild-type DCs. We identify a cross-presentation defect in MyD88-deficient DCs that, when treated with hsp65-P1 fusion protein, results in surface display of fewer SIYRYYGL/class I MHC complexes. Thus, MyD88 plays a role in the developmental maturation of DCs that allows them to prime CD8 T cells through cross-presentation.
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U2 - 10.4049/jimmunol.172.6.3415
DO - 10.4049/jimmunol.172.6.3415
M3 - Article
C2 - 15004140
AN - SCOPUS:1542514777
SN - 0022-1767
VL - 172
SP - 3415
EP - 3421
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -