Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice.
The mucosal lymphocyte integrin alpha E(CD103)beta 7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function. We cloned the murine integrin gene encoding alpha E, localized it to chromosome 11, and generated integrin alpha E-deficient mice. In alpha E-/- mice, intestinal and vaginal IEL numbers were reduced, consistent with the known binding of alpha E beta 7 to E-cadherin expressed on epithelial cells. However, it was surprising that lamina propria T lymphocyte numbers were diminished, as E-cadherin is not expressed in the lamina propria. In contrast, peribronchial, intrapulmonary, Peyer's patch, and splenic T lymphocyte numbers were not reduced in alpha E-deficient mice. Thus, alpha E beta 7 was important for generating or maintaining the gut and vaginal T lymphocytes located diffusely within the epithelium or lamina propria but not for generating the gut-associated organized lymphoid tissues. Finally, the impact of alpha E deficiency upon intestinal IEL numbers was greater at 3-4 wk of life than in younger animals, and affected the TCR alpha beta+ CD8+ T cells more than the gamma delta T cells or the TCR alpha beta+ CD4+CD8- population. These findings suggest that alpha E beta 7 is involved in the expansion/recruitment of TCR alpha beta+ CD8+ IEL following microbial colonization. Integrin alpha E-deficient mice will provide an important tool for studying the role of alpha E beta 7 and of alpha E beta 7-expressing mucosal T lymphocytes in vivo.
Schön
M P
MP
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Arya
A
A
Murphy
E A
EA
Adams
C M
CM
Strauch
U G
UG
Agace
W W
WW
Marsal
J
J
Donohue
J P
JP
Her
H
H
Beier
D R
DR
Olson
S
S
Lefrancois
L
L
Brenner
M B
MB
Grusby
M J
MJ
Parker
C M
CM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D039001:Integrin alpha Chains; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009115:Muridae; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014621:Vagina / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D018960:Hyaluronan Receptors; D039001:Integrin alpha Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; C091367:alpha E integrins