The restriction of influenza A virus replication to mouse respiratory
epithelium means that this host response is anatomically compartmentalized,
on the one hand, to sites of T cell stimulation and proliferation
in the secondary lymphoid tissue and, on the other hand, to the
site of effector T cell function and pathology in the pneumonic
lung. Thus, it is hardly surprising that virus-specific CD8(+)
T cells recovered by bronchoalveolar lavage (BAL) from the infected
respiratory tract seem more "activated" in terms of both cytolytic
activity and cytokine production than those cells isolated from
the spleen. The present analysis uses Affymetrix microarray technology
to compare profiles of gene expression in these two lineage-related,
yet anatomically separate, lymphocyte populations. Ninety differentially
expressed genes were identified for influenza-specific CD8(+)D(b)NP(366)(+)
T cells obtained directly ex vivo by BAL or spleen disruption,
with nine genes being further analyzed by quantitative, real-time
PCR at the population level. Integrin alphaE, for example, was
shown by Affymetrix and real-time mRNA analyses and then by single-cell
PCR and protein staining to be present at a much higher prevalence
on the BAL CD8(+)D(b)NP(366)(+) set. The unpredicted finding,
however, was that mRNA expression for 75% of the 90 genes was
lower in T cells from the BAL than from the spleen. Apparently,
the localization of virus-specific CD8(+) T cells to the site
of virus-induced pathology is associated with a narrowing, or
"focusing," of gene expression that favors enhanced effector function
in the damaged, "high-antigen load" environment of the pneumonic
lung.