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Yoichiro Sano, Bruce R. Ksander, J. Wayne Streilein; Langerhans Cells, Orthotopic Corneal Allografts, and Direct and Indirect Pathways of T-Cell Allorecognition. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1422-1431.
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purpose. To determine after orthotopic corneal allografting the role of
Langerhans cells in activation of T cells via the direct and indirect
pathways of allorecognition and the relationship between these pathways
and the rapidity of graft rejection.
methods. Corneas from eyes of normal mice and from eyes after superficial
cauterization were grafted to eyes of major histocompatibility complex
(MHC) and/or minor histocompatibility (H)–disparate recipient mice.
The grafts were analyzed through time for content of class II
MHC–bearing Langerhans cells and for rejection or acceptance. Graft
recipients were evaluated for acquisition of delayed hypersensitivity
(DH) and cytotoxic T cells (Tc) directed at donor MHC and minor H
results. Langerhans cells migrated more rapidly into epithelium of cauterized
grafts than normal grafts. Unlike normal grafts, the vast majority of
cauterized allografts were rejected within 2 weeks. Normal grafts
induced neither DH nor Tc directed at donor MHC antigens, whereas
cauterized grafts induced both DH and Tc specific for donor MHC. All
grafts induced DH directed at donor minor H antigens, but only rejected
grafts correlated with acquisition of Tc directed at donor minor H
conclusions. The rapidity of orthotopic corneal allograft rejection correlated with
density of Langerhans cells within epithelium and with acquisition of
donor-specific DH and Tc. Although recipient-derived Langerhans cells
promoted minor H-specific, self–MHC-restricted T cells (indirect
pathway) and subacute graft rejection, donor-derived Langerhans cells
promoted early, acute rejection in conjunction with allogeneic
MHC-specific Tc (direct pathway).
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