CD103 expression is required for destruction of pancreatic islet allografts by CD8(+) T cells.
The mechanisms by which CD8 effector populations interact with epithelial layers is a poorly defined aspect of adaptive immunity. Recognition that CD8 effectors have the capacity to express CD103, an integrin directed to the epithelial cell-specific ligand E-cadherin, potentially provides insight into such interactions. To assess the role of CD103 in promoting CD8-mediated destruction of epithelial layers, we herein examined the capacity of mice with targeted disruption of CD103 to reject pancreatic islet allografts. Wild-type hosts uniformly rejected islet allografts, concomitant with the appearance of CD8(+)CD103(+) effectors at the graft site. In contrast, the majority of islet allografts transplanted into CD103(-/-) hosts survived indefinitely. Transfer of wild-type CD8 cells into CD103(-/-) hosts elicited prompt rejection of long-surviving islet allografts, whereas CD103(-/-) CD8 cells were completely ineffectual, demonstrating that the defect resides at the level of the CD8 cell. CD8 cells in CD103(-/-) hosts exhibited normal effector responses to donor alloantigens in vitro and trafficked normally to the graft site, but strikingly failed to infiltrate the islet allograft itself. These data establish a causal relationship between CD8(+)CD103(+) effectors and destruction of graft epithelial elements and suggest that CD103 critically functions to promote intragraft migration of CD8 effectors into epithelial compartments.
Feng
Ye
Y
Division of Transplantation, Department of Surgery, The University of Maryland Medical Center, Baltimore 21201, USA.
Wang
Donghua
D
Yuan
Rongwen
R
Parker
Christina M
CM
Farber
Donna L
DL
Hadley
Gregg A
GA
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D039001:Integrin alpha Chains / Q000235:genetics* / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D017710:Lymphocyte Transfusion; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D039001:Integrin alpha Chains; C091367:alpha E integrins