Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts.
The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T- and B-cell infiltration.
Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Innsbruck Medical University, Innsbruck, Austria.
Theresa
T
Hautz
Bettina G
BG
Zelger
Isam W
IW
Nasr
Gerhard S
GS
Mundinger
Rolf N
RN
Barth
Eduardo D
ED
Rodriguez
Gerald
G
Brandacher
Annemarie
A
Weissenbacher
Bernhard
B
Zelger
Pedro
P
Cavadas
Raimund
R
Margreiter
W P Andrew
WP
Lee
Johann
J
Pratschke
Fadi G
FG
Lakkis
Stefan
S
Schneeberger
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000032:analysis; D064595:Composite Tissue Allografts / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000473:pathology / Q000601:surgery*; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D063987:Hand Transplantation; D006614:Hindlimb / Q000637:transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D042583:Lymphangiogenesis / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology*; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000276:immunology* / Q000473:pathology; D063986:Vascularized Composite Allotransplantation
D015703:Antigens, CD; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents
allograft rejection; lymphoid neogenesis; peripheral node addressin; tertiary lymphoid organs; vascularized composite allotransplantation