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Updated: Aug 14, 2026
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Late dominance of the inflammatory process in murine influenza by gamma/delta + T cells
1Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut.
Abstract:
The inflammatory response in the lungs of mice infected with an influenza A virus consists largely of macrophages and CD3+ T cells. Most T lymphocytes recovered before day 7 after infection express mRNA for the T cell receptor alpha/beta (TCR-alpha/beta), while TCR-gamma/delta mRNA+ cells are found at much higher frequency over the next 7 d. The predominant surface phenotype for the TCR-gamma/delta mRNA+ population is CD3+4-8-TCR-alpha/beta-. Some lymphocytes expressing all the known V gamma genes are found in the inflammatory exudate, but V gamma 2+/V gamma 1+ and V gamma 4+ T cells are present at highest frequency. The response is staged, with maximal numbers of V gamma 4+ cells occurring on day 10 after infection, while the predominant phenotype on day 13 is V gamma 2/V gamma 1+. The emerging peak in numbers of V gamma 4+ lymphocytes is paralleled by increasing numbers of macrophages expressing hsp mRNA. The later maxima found for the V gamma 2+/V gamma 1+ T cells is consistent with the possibility that at least some of these lymphocytes are responding to the hsp+ cells and are functioning to resolve the inflammatory process.
Insights
Influenza A virus infection in mice triggers a lung inflammatory response dominated by macrophages and T cells. Gamma delta T cells, particularly V gamma 4+ and V gamma 2+/V gamma 1+ subsets, play a staged role in this immune response.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Influenza A virus infection induces a significant inflammatory response in the lungs.
- This response involves macrophages and T lymphocytes, with distinct T cell receptor (TCR) populations emerging over time.
Purpose of the Study:
- To characterize the dynamic changes in T cell populations during influenza A virus infection in mice.
- To investigate the specific roles of different T cell receptor gamma delta (TCR-γδ) subsets in the pulmonary inflammatory process.
Main Methods:
- Analysis of inflammatory infiltrates in mouse lungs post-influenza A infection.
- Quantification of T cell populations using mRNA expression for TCR-α/β and TCR-γ/δ.
- Phenotypic characterization of TCR-γ/δ+ lymphocytes (CD3+4-8-TCR-α/β-).
- Assessment of Vγ gene expression (Vγ4, Vγ2/Vγ1) and macrophage heat shock protein (hsp) mRNA levels over time.
Main Results:
- Early infection (before day 7) shows predominantly TCR-α/β+ T cells.
- Later infection (after day 7) reveals a higher frequency of TCR-γ/δ+ T cells, with a CD3+4-8-TCR-α/β- phenotype.
- Specific Vγ subsets exhibit distinct temporal dynamics: Vγ4+ T cells peak around day 10, followed by Vγ2+/Vγ1+ T cells around day 13.
- Increased macrophage hsp mRNA expression correlates with the Vγ4+ T cell peak.
Conclusions:
- The pulmonary immune response to influenza A involves a sequential infiltration of distinct T cell populations.
- TCR-γ/δ+ T cells, particularly Vγ4+ and Vγ2+/Vγ1+ subsets, are key players in the inflammatory and resolution phases.
- The temporal patterns suggest that Vγ4+ T cells may be involved in the early inflammatory phase, while Vγ2+/Vγ1+ T cells might contribute to resolving the inflammation, potentially in response to hsp-expressing macrophages.
