Abstract

Little is known of the population dynamics that influence lymphocyte positioning in virus- infected tissues. To address this issue, we primed animals with Sendai virus (SeV) and harvested cervical lymph nodes (CLN) or spleens 10 days later. Cells were unenriched or enriched for CD3, CD4 or CD8 phenotypes and transferred intraorbitally to GFP-SeV infected mice. Cell positions were then examined by confocal microscopy. Results showed that donor cells were configured in infected tissues with limited overlap. In most infected fields, the mean distance between a donor cell and its nearest neighbor was greater than would be predicted by random uniform distribution. To explain these findings, we hypothesized that a newly resident lymphocyte may instruct expression of unique chemokines/cytokines (c/c) in its immediate vicinity to mark its territory and inhibit co-localization by other cells. In vitro tests supported this hypothesis in that when virus-primed CLN were co-cultured with stroma and SeV, there was a synergistic increase in c/c production. Transwell experiments then showed that cell migration was intricately affected by the c/c milieu at local and distant sites. We therefore propose that a newly-resident lymphocyte in an infected tissue creates a c/c halo to identify and claim its territory. Lymphocyte cross-talk may ensure a spatial distribution of effectors to avoid redundancies and enhance the efficiency with which effector cells clear their virus infected targets.

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