Abstract:
: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 beta1-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 alpha4beta1-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.
journal_name
Int Immunoljournal_title
International immunologyauthors
Lim B,Sutherland RM,Zhan Y,Deliyannis G,Brown LE,Lew AMdoi
10.1093/intimm/dxh367subject
Has Abstractpub_date
2006-02-01 00:00:00pages
291-300issue
2eissn
0953-8178issn
1460-2377pii
dxh367journal_volume
18pub_type
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journal_title:International immunology
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journal_title:International immunology
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pub_type: 杂志文章,评审
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journal_title:International immunology
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journal_title:International immunology
pub_type: 杂志文章
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journal_title:International immunology
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journal_title:International immunology
pub_type: 杂志文章
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journal_title:International immunology
pub_type: 杂志文章
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journal_title:International immunology
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journal_title:International immunology
pub_type: 杂志文章
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