Altered tyrosine phosphorylation via the very late antigen (VLA)/beta1 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 late antigen (VLA)/beta1 with anti-CD29 monoclonal antibody (MoAb), or interactions with extracellular matrix (ECM) proteins through VLA/beta1, failed to induce T-cell costimulation via the CD3/T cell receptor (TCR) pathway for over 1 year after allogeneic bone marrow transplantation (allo-BMT), although normal CD29 and CD3 expression was observed after 3 months following allo-BMT. Molecular analysis revealed altered tyrosine phosphorylation of cellular proteins by the solid-phase cross-linking of VLA/beta1 molecules in T cells from patients after allo-BMT. In T cells from early allo-BMT patients (<4 months), various sizes of highly tyrosine phosphorylated proteins were observed as high background even without the stimulation through VLA/beta1 integrin. The high tyrosine phosphorylation pattern gradually disappeared and it was finally returned to normal tyrosine phosphorylation patterns by 2 years after BMT. Interestingly, poor expression of focal adhesion kinase (pp125FAK), a VLA/beta1-mediated signaling molecule, was observed within 1 year after BMT. These results suggest that these molecular defects appear to be implicated in the impaired VLA/beta1-mediated signaling in T cells from patients after allo-BMT, and it could explain, in part, the persistent immunoincompetent state after allo-BMT at least 1 year.
Sato
T
T
Division of Tumor Immunology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Ohashi
Y
Y
Tachibana
K
K
Soiffer
R J
RJ
Ritz
J
J
Morimoto
C
C
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D006801:Humans; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000276:immunology; D016023:Integrins / Q000276:immunology*; D008875:Middle Aged; D010766:Phosphorylation; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D016029:Receptors, Very Late Antigen / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous; D014443:Tyrosine
D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D014443:Tyrosine