Lymphotoxin controls |[agr]|E|[bgr]|7-integrin expression by peripheral CD8|[plus]| T cells

Lymphotoxin (LT)-, 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 E7-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 7-integrin expression by peripheral CD8+ T cells or a failure of thymic emigration of CD8+ 7-integrinhigh T cells, 7-integrin was examined on recent thymic emigrants (RTE). When analysed within 16 h after leaving the thymus CD4–CD8+ RTE in both LT-–/– and wild type (wt) mice remained 7-integrinhigh and were indistinguishable. However, within 3–5 days, emigration loss of 7-integrin became evident in LT-–/– mice. Despite this loss, the proportion of thymically derived TCR+ T-cell populations in the intestinal epithelium, an important target tissue of CD8+ E7-integrinhigh T cells, was increased in the absence of LT-. In contrast, B cells were detectable only rarely in the intestinal tissue of LT-–/– mice. The expression of E-Cadherin remained unchanged. These results indicate that a LT--dependent process maintains a high level of E7-integrin expression by peripheral CD8+ T cells, and with this control mechanism LT- may help to regulate CD8+ T-cell numbers in the tissues.