Limits...
CD103 expression is required for destruction of pancreatic islet allografts by CD8(+) T cells.

Feng Y, Wang D, Yuan R, Parker CM, Farber DL, Hadley GA - J. Exp. Med. (2002)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplantation, Department of Surgery, The University of Maryland Medical Center, Baltimore 21201, USA.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

CD8 cells in CD103-deficient hosts traffic normally to the graft site. Equal numbers (5 × 106) of purified CD8 cells from CD103−/− (Thy1.1−/1.2+) and CD103+/+ (Thy1.1+/1.2−) donors were transferred into wild-type (Thy1.1+/Thy1.2+) hosts which were subsequently transplanted with A/J islet allografts. At the time of rejection, GILs were stained for three-color FACS® analyses with anti-Thy1.1-PE and anti-Thy1.2-FITC in combination with anti-CD8a-CyChrome. Data shown are for electronically gated CD8+ lymphocytes. The quadrant on right shows the relative positions of wild-type and CD103−/− cells in the density plot on left. Data shown are representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2194029&req=5

fig5: CD8 cells in CD103-deficient hosts traffic normally to the graft site. Equal numbers (5 × 106) of purified CD8 cells from CD103−/− (Thy1.1−/1.2+) and CD103+/+ (Thy1.1+/1.2−) donors were transferred into wild-type (Thy1.1+/Thy1.2+) hosts which were subsequently transplanted with A/J islet allografts. At the time of rejection, GILs were stained for three-color FACS® analyses with anti-Thy1.1-PE and anti-Thy1.2-FITC in combination with anti-CD8a-CyChrome. Data shown are for electronically gated CD8+ lymphocytes. The quadrant on right shows the relative positions of wild-type and CD103−/− cells in the density plot on left. Data shown are representative of three independent experiments.

Mentions: An adoptive transfer model was devised to assess the efficiency with which CD103-deficient CD8 effectors traffic to the graft site. In this model, equal numbers (5 × 106) of purified CD8 cells from CD103−/− (Thy1.1−/1.2+) and CD103+/+ (Thy1.1+/1.2−) donors were transferred into syngeneic wild-type (Thy1.1+/Thy1.2+) hosts which subsequently received A/J islet allografts. Three-color FACS® of GILs harvested at the time of early rejection (BG > 200 mg/dL) were then used to quantitate relative numbers of transferred CD8 populations which successfully trafficked to the graft site. As shown in Fig. 5 , CD103-deficient CD8 cells trafficked to the graft with efficiency comparable to that of wild-type CD8 cells. In three independent experiments, 18.7 ± 1.4% (mean ± SE) of the transferred cell population was of CD103−/− origin as compared with 20.6 ± 5.8% of CD103+/+ origin. Importantly, CD8 cells isolated from such grafts were devoid of naive (CD62LhiCD44lo) CD8 cells (unpublished data), thereby excluding the trivial possibility that the graft-associated CD8 cells derived from contaminating peripheral blood. Thus, these data demonstrate that CD103 expression is not required for effective activation of CD8 cells or trafficking of the resulting CD8 effectors to the general graft site.


CD103 expression is required for destruction of pancreatic islet allografts by CD8(+) T cells.

Feng Y, Wang D, Yuan R, Parker CM, Farber DL, Hadley GA - J. Exp. Med. (2002)

CD8 cells in CD103-deficient hosts traffic normally to the graft site. Equal numbers (5 × 106) of purified CD8 cells from CD103−/− (Thy1.1−/1.2+) and CD103+/+ (Thy1.1+/1.2−) donors were transferred into wild-type (Thy1.1+/Thy1.2+) hosts which were subsequently transplanted with A/J islet allografts. At the time of rejection, GILs were stained for three-color FACS® analyses with anti-Thy1.1-PE and anti-Thy1.2-FITC in combination with anti-CD8a-CyChrome. Data shown are for electronically gated CD8+ lymphocytes. The quadrant on right shows the relative positions of wild-type and CD103−/− cells in the density plot on left. Data shown are representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194029&req=5

fig5: CD8 cells in CD103-deficient hosts traffic normally to the graft site. Equal numbers (5 × 106) of purified CD8 cells from CD103−/− (Thy1.1−/1.2+) and CD103+/+ (Thy1.1+/1.2−) donors were transferred into wild-type (Thy1.1+/Thy1.2+) hosts which were subsequently transplanted with A/J islet allografts. At the time of rejection, GILs were stained for three-color FACS® analyses with anti-Thy1.1-PE and anti-Thy1.2-FITC in combination with anti-CD8a-CyChrome. Data shown are for electronically gated CD8+ lymphocytes. The quadrant on right shows the relative positions of wild-type and CD103−/− cells in the density plot on left. Data shown are representative of three independent experiments.
Mentions: An adoptive transfer model was devised to assess the efficiency with which CD103-deficient CD8 effectors traffic to the graft site. In this model, equal numbers (5 × 106) of purified CD8 cells from CD103−/− (Thy1.1−/1.2+) and CD103+/+ (Thy1.1+/1.2−) donors were transferred into syngeneic wild-type (Thy1.1+/Thy1.2+) hosts which subsequently received A/J islet allografts. Three-color FACS® of GILs harvested at the time of early rejection (BG > 200 mg/dL) were then used to quantitate relative numbers of transferred CD8 populations which successfully trafficked to the graft site. As shown in Fig. 5 , CD103-deficient CD8 cells trafficked to the graft with efficiency comparable to that of wild-type CD8 cells. In three independent experiments, 18.7 ± 1.4% (mean ± SE) of the transferred cell population was of CD103−/− origin as compared with 20.6 ± 5.8% of CD103+/+ origin. Importantly, CD8 cells isolated from such grafts were devoid of naive (CD62LhiCD44lo) CD8 cells (unpublished data), thereby excluding the trivial possibility that the graft-associated CD8 cells derived from contaminating peripheral blood. Thus, these data demonstrate that CD103 expression is not required for effective activation of CD8 cells or trafficking of the resulting CD8 effectors to the general graft site.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplantation, Department of Surgery, The University of Maryland Medical Center, Baltimore 21201, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus