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Altered Tyrosine Phosphorylation Via the Very Late Antigen (VLA)/beta 1 Integrin Stimulation Is Associated With Impaired T-Cell Signaling Through VLA-4 After Allogeneic Bone Marrow Transplantation

Toshiya Sato, Yoshiyuki Ohashi, Kouichi Tachibana, Robert J. Soiffer, Jerome Ritz, and Chikao Morimoto

From the Divisions of Tumor Immunology and Hematologic Malignancies, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA.

Our previous study showed that the cross-linking of very late antigen (VLA)/beta 1 with anti-CD29 monoclonal antibody (MoAb), or interactions with extracellular matrix (ECM) proteins through VLA/beta 1, 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/beta 1 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/beta 1 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/beta 1-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/beta 1-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.

Blood, Vol. 90 No. 10 (November 15), 1997: pp. 4222-4229
© 1997 by The American Society of Hematology.


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