Histopathologic characterization of mild rejection (grade I) in skin biopsies of human hand allografts

Mild skin rejection is a common observation in reconstructive transplantation. To enlighten the role of this inflammatory reaction we investigated markers for cellular and antibody mediated rejection, adhesion molecules and tolerance markers. Forty-seven skin biopsies (rejection grade I) of human hand allografts were investigated by immunohistochemistry (CD3, CD4, CD8, CD20, CD68, C4d, LFA-1, ICAM-1, E-selectin, P-selectin, VE-cadherin, HLA-DR, IDO, and Foxp3). Expression was read with respect to time after transplant. The infiltrate was mainly comprised of CD3+T-lymphocytes. Among these, CD8+cells were more prominent than CD4+cells. CD20+B-lymphocytes were sparse and CD68+macrophages were found in some, but not all samples (approximately 10% of the infiltrate). The CD4/CD8-ratio was increased after the first year. C4d staining was mainly positive in samples at time-points later than 1 year. Adhesion molecules LFA-1, ICAM-1, E-selectin, P-selectin, and VE-cadherin were found upregulated, and for P-selectin, expression increased with time after transplant. IDO expression was strongest at 3 months-1 year post-transplant and a tendency toward more Foxp3+ cells at later time points was observed. Mild skin rejection after hand transplantation presents with a T-cell dominated dermal cell infiltrate and upregulation of adhesion molecules. The role of C4d expression after year one remains to be elucidated.