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International Immunology Advance Access originally published online on December 16, 2005
International Immunology 2006 18(2):291-300; doi:10.1093/intimm/dxh367
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Targeting CD45RB alters T cell migration and delays viral clearance

Bock Lim1,*, Robyn M. Sutherland2,*, Yifan Zhan2, Georgia Deliyannis1, Lorena E. Brown1 and Andrew M. Lew2

1 Department of Microbiology and Immunology and Cooperative Research Centre for Vaccine Technology, University of Melbourne, Royal Parade, Melbourne 3010, Australia
2 Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne 3050, Australia

Correspondence to: A. M. Lew; E-mail: lew{at}wehi.edu.au. L. E. Brown; E-mail: l.brown{at}microbiology.unimelb.edu.au

CD45 is a receptor tyrosine phosphatase essential for TCR signaling. One isoform, CD45RB, is down-regulated in memory cells and targeting CD45RB with a specific antibody has been shown to inhibit graft rejection. Its role in immunity to infection, however, has not been tested. Here, we report the effect of anti-CD45RB antibody treatment on the induction of anti-influenza CD8+ T cells and viral clearance. Anti-CD45RB-treated mice had delayed pulmonary viral clearance compared with untreated mice whose infection was completely cleared by day 8 post-infection. In anti-CD45RB-treated mice, the total CD4+ and CD8+ T cell numbers in both the lungs and mediastinal nodes were substantially reduced at days 5 and 8; this effect was less marked for the spleen. CD8+ T cells specific for influenza virus were also reduced compared with the control group in all three organs at day 8. By day 11, when both treated and control groups showed no virus remaining in the lungs, specific CD8+ T cell numbers were at similar low levels. Homing to lymph nodes and lung of dye-labeled T cells was greatly inhibited (by >80%) by anti-CD45RB treatment. This reduced homing corresponded with reduced CD62L and ß1-integrin expression in both uninfected and infected mice. Since CD62L plays a critical role in homing lymphocytes to lymph nodes, and high levels of CD62L and {alpha}4ß1-integrin are expressed by lymphocytes that home to bronchus-associated lymphoid tissue, we suggest that reduced expression of these molecules is a key explanation for the delay in immune responses.

Keywords: CD45, CTL, homing, influenza, trafficking

* These authors contributed equally.

Transmitting editor: E. Simpson


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