Lymphotoxin controls alphaEbeta7-integrin expression by peripheral CD8+ T cells.
Lymphotoxin (LT)-alpha, a member of the TNF family, is recognized as an important mediator in different aspects of lymphoid organ development. Targeted disruption of this molecule resulted in a substantial reduction in the proportion of alphaEbeta7-integrin(high) CD8+ T cells detectable in peripheral lymphoid organs. This defect, however, was not observed on mature CD4-CD8+ thymocytes. To determine whether this was due to downregulation of beta7-integrin expression by peripheral CD8+ T cells or a failure of thymic emigration of CD8+ beta7-integrin(high) T cells, beta7-integrin was examined on recent thymic emigrants (RTE). When analysed within 16 h after leaving the thymus CD4-CD8+ RTE in both LT-alpha-/- and wild type (wt) mice remained beta7-integrin(high) and were indistinguishable. However, within 3-5 days, emigration loss of beta7-integrin became evident in LT-alpha-/- mice. Despite this loss, the proportion of thymically derived alphabetaTCR+ T-cell populations in the intestinal epithelium, an important target tissue of CD8+ alphaEbeta7-integrin(high) T cells, was increased in the absence of LT-alpha. In contrast, B cells were detectable only rarely in the intestinal tissue of LT-alpha-/- mice. The expression of E-Cadherin remained unchanged. These results indicate that a LT-alpha-dependent process maintains a high level of alphaEbeta7-integrin expression by peripheral CD8+ T cells, and with this control mechanism LT-alpha may help to regulate CD8+ T-cell numbers in the tissues.
Gabor
M J
MJ
Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia.
Sedgwick
J D
JD
Lemckert
F A
FA
Godfrey
D I
DI
Körner
H
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015820:Cadherins / Q000378:metabolism; D017690:Cell Transplantation; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis*; D007421:Intestine, Small / Q000166:cytology; D008233:Lymphotoxin-alpha / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D015820:Cadherins; D016023:Integrins; D008233:Lymphotoxin-alpha; C070709:integrin alphaEbeta7