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Epidermal Langerhans Cells Promote Skin Allograft Rejection in Mice With NF‐κB‐impaired T Cells
Author(s) -
Molinero L. L.,
Zhou P.,
Wang Y.,
Harlin H.,
Kee B.,
Abraham C.,
Alegre M. L.
Publication year - 2008
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2007.02038.x
Subject(s) - medicine , transplantation , t cell , immunology , langerhans cell , cancer research , immune system
T cells play a major role in the acute rejection of transplanted organs. Using mice transgenic for a T‐cell‐restricted NF‐κB super‐repressor (IκBαΔN‐Tg mice), we have previously shown that T‐cell‐NF‐κB is essential for the acute rejection of cardiac but not skin allografts. In this study, we investigated the mechanism by which skin grafts activate IκBαΔN‐Tg T cells. Rejection was not due to residual T‐cell‐NF‐κB activity as mice with p50/p52 −/− T cells successfully rejected skin grafts. Rather, skin but not cardiac allografts effectively induced proliferation of graft‐specific IκBαΔN‐Tg T cells. Rejection of skin grafts by IκBαΔN‐Tg mice was in part dependent on the presence of donor Langerhans cells (LC), a type of epidermal dendritic cells (DC), as lack of LC in donor skin grafts resulted in prolongation of skin allograft survival and injection of LC at the time of cardiac transplantation was sufficient to promote cardiac allograft rejection by IκBαΔN‐Tg mice. Our results suggest that LC allow NF‐κB‐impaired T cells to reach an activation threshold sufficient for transplant rejection. The combined blockade of T‐cell‐NF‐κB with that of alternative pathways allowing activation of NF‐κB‐impaired T cells may be an effective strategy for tolerance induction to highly immunogenic organs.