During human thymic development, beta(1) integrins regulate adhesion, motility, and the outcome of RHAMM/hyaluronan engagement

During human thymic differentiation, interactions between fibronectin (Fn)/ beta(1) integrins and hyaluronan (HA)/RHAMM control motility and Fn/beta(1) integrins mediate spontaneous Fn-dependent adhesion, Multinegative (MN, CD 3(-)4(-)8(-)) thymocytes exhibit strong spontaneous adherence to Fn (75%) t hat was efficiently inhibited by anti-alpha(5)beta(1) and only weakly inhib ited by anti-alpha(4)beta(1). The relatively weak adherence of unfractionat ed thymocytes to Fn required both alpha(4)beta(1) and alpha(5)beta(1). Vide o time-lapse microscopy indicates that a subset of thymocytes also undergo spontaneous Fn-dependent motility mediated by alpha(5)beta(1), alpha(4)beta (1) and the HA-receptor RHAMM, but not by CD44. The loss of motility after hyaluronidase treatment of thymocytes indicated that motility is strongly d ependent on HA. Of motile cells, 55% were DP, 19% were DN, and 24% were CD4 (+)SP, but only 1% were CD8(+)SP. Overall, for BIN thymocytes, beta(1) inte grin mediated Fn-adhesion, but after expression of CD4/CD8, beta(1) integri ns mediated Fn-dependent motility, Treatment with the activating anti-beta( 1) mAb QE.2E5 inhibited thymic motility and converted otherwise nonadherent thymocytes to an adherent state. High-avidity interactions via integrins a ppear to supercede the motogenicity of RHAMM and HA, suggesting that integr in avidity may regulate RHAMM, During thymic development, changes in adhesi on or motility appear to be mediated by integrin avidity modulation.