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Subverting lymph node trafficking by treatment with the Mel-14 monoclonal antibody to L-selectin does not prevent an
1Department of Biology, University of California San Diego, La Jolla 92093, USA.
Abstract:
A single 250-micrograms dose of the Mel-14 mAb to L-selectin greatly diminished the extent of L-selectin expression on lymphocytes and decreased (60 to 90%) the massive cellular recruitment to the cervical and mediastinal lymph nodes that follows intranasal infection of naive C57BL/6 mice with Sendai virus. The numbers of CD8+ CTL precursors in the mediastinal lymph nodes were considerably reduced on day 7, when compared with virus-infected mice given a control rat IgG2a, but potent CTL effectors were present in the lungs of both groups by day 10 after infection, and the overall magnitude of CTL precursor generation was not obviously compromised. The early dominance of Sendai virus-specific IgM Ab-forming cells was prolonged in the Mel-14-treated mice, whereas plasma cells producing virus-specific IgA were abnormally prominent in the lymph nodes but not in the spleen. The kinetics of virus-specific Ab-forming cells generation and the serum Ab response for the various IgG isotypes were also delayed. Thus, though L-selectin is clearly important for the localization of naive lymphocytes to regional lymph nodes, the Mel-14-treated mouse can still deal effectively with a virus that causes productive infection only in the respiratory tract. The spleen, where L-selectin does not determine lymphocyte trafficking, is a major site for the compensatory T cell and B cell responses.
Insights
Blocking L-selectin with Mel-14 mAb reduces lymphocyte migration to lymph nodes during Sendai virus infection. However, mice still mount effective immune responses, particularly in the spleen.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- L-selectin mediates lymphocyte homing to lymph nodes.
- Sendai virus infection triggers significant cellular recruitment to lymph nodes.
- Understanding lymphocyte trafficking is crucial for immune response modulation.
Purpose of the Study:
- To investigate the role of L-selectin in immune responses to intranasal Sendai virus infection.
- To determine the impact of L-selectin blockade on cellular recruitment and adaptive immunity.
- To explore compensatory immune mechanisms in L-selectin deficient conditions.
Main Methods:
- Administration of anti-L-selectin antibody (Mel-14 mAb) in C57BL/6 mice.
- Intranasal inoculation with Sendai virus.
- Analysis of lymphocyte populations, cytotoxic T lymphocyte (CTL) precursors, and antibody-forming cells in lymphoid organs and lungs.
- Flow cytometry and antibody assays.
Main Results:
- Mel-14 mAb treatment significantly reduced lymphocyte recruitment to cervical and mediastinal lymph nodes.
- CD8+ CTL precursor numbers were reduced in lymph nodes, but effector CTLs were present in the lungs.
- Early IgM dominance was prolonged, while IgA plasma cells increased in lymph nodes; IgG responses were delayed.
- The spleen showed compensatory T and B cell responses, independent of L-selectin-mediated trafficking.
Conclusions:
- L-selectin is critical for naive lymphocyte localization to lymph nodes during Sendai virus infection.
- Despite impaired lymph node homing, effective anti-viral immunity can be mounted.
- The spleen serves as a key site for compensatory immune responses when L-selectin-dependent trafficking is blocked.