TY - JOUR
T1 - CD4 T cell-dependent conditioning of dendritic cells to produce IL-12 results in CD8-mediated graft rejection and avoidance of tolerance
AU - Filatenkov, Alexander A.
AU - Jacovetty, Erica L.
AU - Fischer, Ursula B.
AU - Curtsinger, Julie M.
AU - Mescher, Matthew F.
AU - Ingulli, Elizabeth
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - Rejection of ectopic heart transplants expressing OVA requires OVA-specific CD4 and CD8 T cells. In the absence of CD4 T cells, OVA-specific CD8 T cells proliferate and migrate to the graft, but fail to develop cytolytic functions. With CD4 T cells present, clonal expansion of the CD8 T cells is only marginally increased but the cells now develop effector functions and mediate rapid graft rejection. In the presence of CD4 T cells, Ag and B7 levels do not increase on dendritic cells but IL-12 production is up-regulated, and this requires CD154 expression on the CD4 T cells. OVA-specific CD8 T cells lacking the IL-12 receptor fail to differentiate or mediate graft rejection even when CD4 T cells are present. Thus, CD4 T cells condition dendritic cells by inducing the production of IL-12, which is needed as the "third signal" for CD8 T cell differentiation and avoidance of tolerance.
AB - Rejection of ectopic heart transplants expressing OVA requires OVA-specific CD4 and CD8 T cells. In the absence of CD4 T cells, OVA-specific CD8 T cells proliferate and migrate to the graft, but fail to develop cytolytic functions. With CD4 T cells present, clonal expansion of the CD8 T cells is only marginally increased but the cells now develop effector functions and mediate rapid graft rejection. In the presence of CD4 T cells, Ag and B7 levels do not increase on dendritic cells but IL-12 production is up-regulated, and this requires CD154 expression on the CD4 T cells. OVA-specific CD8 T cells lacking the IL-12 receptor fail to differentiate or mediate graft rejection even when CD4 T cells are present. Thus, CD4 T cells condition dendritic cells by inducing the production of IL-12, which is needed as the "third signal" for CD8 T cell differentiation and avoidance of tolerance.
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U2 - 10.4049/jimmunol.174.11.6909
DO - 10.4049/jimmunol.174.11.6909
M3 - Article
C2 - 15905533
AN - SCOPUS:18944367801
SN - 0022-1767
VL - 174
SP - 6909
EP - 6917
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -