Lymphotoxin controls alpha(E)beta 7-integrin expression by peripheral CD8(+) T cells
Gabor, MJ and Sedgwick, JD and Lemckert, FA and Godfrey, DI and Korner, H, Lymphotoxin controls alpha(E)beta 7-integrin expression by peripheral CD8(+) T cells, Immunology and Cell Biology, 79, (4) pp. 323-331. ISSN 0818-9641 (2001) [Refereed Article]
Lymphotoxin (LT)-α, 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 αEβ7-integrinhigh 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 β7-integrin expression by peripheral CD8+ T cells or a failure of thymic emigration of CD8+ β7-integrinhigh T cells, β7-integrin was examined on recent thymic emigrants (RTE). When analysed within 16 h after leaving the thymus CD4-CD8+ RTE in both LT-α-/- and wild type (wt) mice remained β7-integrinhigh and were indistinguishable. However, within 3-5 days, emigration loss of β7-integrin became evident in LT-α-/- mice. Despite this loss, the proportion of thymically derived αβTCR+ T-cell populations in the intestinal epithelium, an important target tissue of CD8+ αEβ7-integrinhigh T cells, was increased in the absence of LT-α. In contrast, B cells were detectable only rarely in the intestinal tissue of LT-α-/- mice. The expression of E-Cadherin remained unchanged. These results indicate that a LT-α-dependent process maintains a high level of αEβ7-integrin expression by peripheral CD8+ T cells, and with this control mechanism LT-α may help to regulate CD8+ T-cell numbers in the tissues.