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Targeting CD45RB alters T cell migration and delays viral clearance
R.M. Sutherland,
Y. Zhan, A.M. Lew, in collaboration with B. Lim, G. Deliyannis, L.E. Brown, Department of Microbiology and Immunology, The University of Melbourne
CD45 tyrosine phosphatase is essential for TCR signalling. One isoform, CD45RB, can be targeted with antibody thereby inhibiting graft rejection. However, the consequences for immunity to infection have not been assessed. We showed influenza virus clearance, albeit delayed, from lungs of anti-CD45RB–treated mice compared with untreated mice. Total virus-specific CD8 T cells were initially reduced in the lung and draining lymph node of treated mice. Total T cells were dramatically reduced in the lymph node, as was dye-labelled T cell homing to this site. Reduced homing corresponded with reduced CD62L and beta-1-integrin expression, and provides a basis for the delayed immune response .
Mature and immature T cells differ in the regulation of GITR upon TCR ligation
Y. Zhan, J.L. Brady, A.M. Lew, in collaboration with P. Bouillet, A. Strasser, Molecular Genetics of Cancer Division; G.M. Davey, W.R. Heath, Immunology Division
Mature T cells survive, grow and proliferate whereas immature T cells die immediately upon TCR engagement. Why their fate differs following TCR engagement is not entirely clear. There may be differential regulation of TCR-mediated survival signals by mature T cells and immature T cells. Using TCR transgenic mice specific for ovalbumin, we demonstrated that upon injection of antigenic peptide, CD4+ CD8- thymocytes, a mature type of T cell in the thymus, upregulated anti-apoptotic glucocorticoid-induced TNF receptor (GITR). In contrast, immature CD4+ CD8+ thymocytes failed to upregulate GITR upon TCR engagement.
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