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Lymphotoxin controls alpha(E)beta 7-integrin expression by peripheral CD8(+) T cells
journal contributionposted on 2023-05-17, 07:45 authored by Gabor, MJ, Sedgwick, JD, Lemckert, FA, Godfrey, DI, Heinrich KornerHeinrich Korner
Lymphotoxin (LT)-Î±, 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 Î±EÎ²7-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 Î²7-integrin expression by peripheral CD8+ T cells or a failure of thymic emigration of CD8+ Î²7-integrinhigh T cells, Î²7-integrin was examined on recent thymic emigrants (RTE). When analysed within 16 h after leaving the thymus CD4-CD8+ RTE in both LT-Î±-/- and wild type (wt) mice remained Î²7-integrinhigh and were indistinguishable. However, within 3-5 days, emigration loss of Î²7-integrin became evident in LT-Î±-/- mice. Despite this loss, the proportion of thymically derived Î±Î²TCR+ T-cell populations in the intestinal epithelium, an important target tissue of CD8+ Î±EÎ²7-integrinhigh T cells, was increased in the absence of LT-Î±. In contrast, B cells were detectable only rarely in the intestinal tissue of LT-Î±-/- mice. The expression of E-Cadherin remained unchanged. These results indicate that a LT-Î±-dependent process maintains a high level of Î±EÎ²7-integrin expression by peripheral CD8+ T cells, and with this control mechanism LT-Î± may help to regulate CD8+ T-cell numbers in the tissues.
Publication titleImmunology and Cell Biology
Department/SchoolMenzies Institute for Medical Research
PublisherBlackwell Publishing Asia
Place of publication54 University St, P O Box 378, Carlton, Australia, Victoria, 3053