Altered Tyrosine Phosphorylation Via the Very Late Antigen (VLA)/b1 Integrin Stimulation Is Associated With Impaired T-Cell Signaling Through VLA-4 After Allogeneic Bone Marrow Transplantation

Our previous study showed that the cross-linking of very without the stimulation through VLA/b1 integrin. The high late antigen (VLA)/b1 with anti-CD29 monoclonal antibody tyrosine phosphorylation pattern gradually disappeared and (MoAb), or interactions with extracellular matrix (ECM) proit was finally returned to normal tyrosine phosphorylation teins through VLA/b1, failed to induce T-cell costimulation patterns by 2 years after BMT. Interestingly, poor expression via the CD3/T cell receptor (TCR) pathway for over 1 year of focal adhesion kinase (pp125), a VLA/b1-mediated sigafter allogeneic bone marrow transplantation (allo-BMT), alnaling molecule, was observed within 1 year after BMT. though normal CD29 and CD3 expression was observed after These results suggest that these molecular defects appear 3 months following allo-BMT. Molecular analysis revealed to be implicated in the impaired VLA/b1-mediated signaling altered tyrosine phosphorylation of cellular proteins by the in T cells from patients after allo-BMT, and it could explain, solid-phase cross-linking of VLA/b1 molecules in T cells from in part, the persistent immunoincompetent state after allopatients after allo-BMT. In T cells from early allo-BMT paBMT at least 1 year. tients (Ú4 months), various sizes of highly tyrosine phosq 1997 by The American Society of Hematology. phorylated proteins were observed as high background even