Transendothelial migration confers a survival advantage to activated T lymphocytes
Borthwick NJ., Yong KL., Salmon M., Buckley C., Akbar AN.
Primed CD45RO+,CD45RBlo T lymphocytes are prone to apoptosis in vitro but accumulate within the inflamed synovium of patients with rheumatoid arthritis. We hypothesise that when these cells migrate into tissue they receive signals that can influence their survival. To test this we investigated the effect of migration over HUVEC on the apoptosis of IL-2 dependent T cell lines. After 18 hours culture on HUVEC >95% of the T cells migrated into the lower well of a Transwell. These migrated cells showed an enhanced survival compared to cells cultured in medium alone (survival 48 hours; non-migrated 33.1±8.1%, migrated 56.8± 9.2%; p<0.001). Migration per se was important for this enhanced survival as cells incubated in the lower well of the Transwell showed no survival advantage. Additionally, T cells migrating across fibronectin coated filters showed no survival advantage suggesting that cellular interactions are important for the enhanced survival. Neutralising antibodies to LFA-1 reduced transmigration but had no effect on cell survival however, these antibodies were able to prevent apoptosis after activation through the TCR. Furthermore, immobilised ICAM-1 alone partially prevented T cell apoptosis. Thus, signals through LFA-1 may be important in migration conferred survival.