Non-random lymphocyte distribution among virus-infected cells of the respiratory tract.

The rules of T cell positioning within virus-infected respiratory tract tissues are poorly understood. We therefore marked cervical lymph node or spleen cells from Sendai virus (SeV) primed mice and transferred lymphocytes to animals infected with SeV expressing an enhanced green fluorescent protein (SeV-eGFP). Confocal imaging showed that when T cells entered a field of infected respiratory tract epithelium, they assumed a spatial distribution that maximized distances between each donor cell and its nearest neighbor. We therefore hypothesized that lymphocytes repelled one another by altering their chemokine/cytokine microenvironment. Subsequent in vitro tests confirmed that when SeV-primed lymphocytes were co-cultured with infected respiratory tract stroma, there was a profound upregulation of chemokines including RANTES, CXCL9, CXCL10, and CCL2. Based on these data, we propose that newly resident lymphocytes within virus-infected respiratory tract tissues may create halos of chemokines/cytokines to mark their territories; lymphocyte cross-talk may then inhibit cell overlap and redundancy to expedite virus clearance.