The epithelial cell-specific integrin, CD103 (alpha E integrin), defines a novel subset of alloreactive CD8+ CTL.
The interaction of CD8+CTL with epithelial layers is an important but poorly defined aspect of organ allograft rejection. We herein report that CD103 (formerly alpha E integrin), a known receptor for the epithelial cell-specific ligand E-cadherin, is expressed by a major subset of CD8 + CTL elicited in response to allogeneic renal epithelial cells (REC). In contrast, CD103 was expressed poorly on CD8 + CTL generated in the conventional manner by stimulation with allogeneic leukocytes, although expression could be dramatically up-regulated by supplementing cultures with REC or exogenous TGF-beta 1. That TGF-beta controls the expression of CD103 on CD8+ CTL was further supported by the capacity of anti-TGF-beta mAb to block the generation of such cells in anti-REC cultures. Clonal analyses of anti-REC cultures revealed that individual CD8+ CTL clones were discretely CD103+ or CD103-, nd maintained their respective phenotypes independently of the cell type used for clonal restimulation. In a mouse model of graft-vs-host disease, 16.4 +/- 2.7% of CD8 cells that infiltrated host kidneys were CD103+ (n = 4). CD8 kidney-infiltrating lymphocytes were predominantly of donor origin and displayed an activated/memory phenotype (CD62L-, CD44high), consistent with expression of CD103 on a CD8 effector subset elicited in vivo following allogeneic transplantation. Taken together, the present data demonstrate that CD103 identifies a novel CD8 effector subset and, moreover, that such cells may comprise a significant component of the response to allogeneic tissues. The potential for CD103+ CTL as an important effector mechanism in organ allograft rejection, and more generally, as a mechanistic basis for tissue-specific immune phenomena, is discussed.
Hadley
G A
GA
Department of Surgery, University of Maryland Medical School, Baltimore 21201, USA. GHADLEY@SURGERY2.AB.UMD.EDU
Bartlett
S T
ST
Via
C S
CS
Rostapshova
E A
EA
Moainie
S
S
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D039001:Integrin alpha Chains; D016023:Integrins / Q000276:immunology*; D007668:Kidney / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; D016212:Transforming Growth Factor beta; C091367:alpha E integrins