Kinetics of leukocyte and myeloid cell traffic in the murine corneal allograft response

Background. Little information exists on the trafficking of myeloid and lym phoid cells between the transplanted cornea and the secondary lymphoid tiss ue. This study reports on changes in the cornea and the draining lymph node (DLN) from the time of graft emplacement. Methods. Using a mouse corneal graft model (C57BL/ 10Sn to BALB/c), eyes an d submandibular DLN were examined by immunohistochemistry and three-color f low cytometry for evidence of T cell activation and dendritic cell (DC) con ditioning (up-regulation of costimulatory molecules) at various times (15 m in to 24 days; n=4 for each time). Results. In the DLN, early (2 hr) DC conditioning was sustained throughout allograft rejection whereas a remarkable drop in percentage of activated CD 4(+) and CDS' T cells (P <0.001) was followed by a biphasic rise in activat ed CD4(+) and, to a lesser extent, CD8(+) T cells (24 hr, P <0.001 and 6 da ys, P <0.01). CD11b(+) and MOMA-2(+) macrophages, MHC Class II+ cells, CD86 (+) DC, and neutrophils were the earliest cells infiltrating the cornea (at 24 hr), whereas T cells appeared after 2 days, with CD4(+) T cells being c onfined largely to the graft recipient border. Conclusions. Immediate and rapid changes in T cell and DC populations in th e DLN correlate with the type of cellular infiltration in the corneal graft . The data are consistent with a model in which CD4(+) T cell help for CD8( +) cytotoxic T cells could be provided by sequential two-way activation of T cells and DC in the DLN. The majority of cells infiltrating the graft wer e macrophages and neutrophils, with fewer DC and T cells.