The TNF superfamily of cytokines play an important role in T cell activation and inflammation. Sustained expression of lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T cells (LIGHT) (TNFSF14) causes a pathological intestinal inflammation when constitutively expressed by mouse T cells. In this study, we characterized LIGHT expression on activated human T cell subsets in vitro and demonstrated a direct proinflammatory effect on regulation of IFN-γ. LIGHT was induced in memory CD45RO CD4+ T cells and by IFN-γ-producing CD4+ T cells. Kinetic analysis indicated rapid induction of LIGHT by human lamina propria T cells, reaching maximal levels by 2–6 h, whereas peripheral blood or lymph node-derived T cells required 24 h. Further analysis of intestinal specimens from a 41 patient cohort by flow cytometry indicated membrane LIGHT induction to higher peak levels in lamina propria T cells from the small bowel or rectum but not colon, when compared with lymph node or peripheral blood. Independent stimulation of the LIGHT receptor, herpesvirus entry mediator, induced IFN-γ production in lamina propria T cells, while blocking LIGHT inhibited CD2-dependent induction of IFN-γ synthesis, indicating a role for LIGHT in the regulation of IFN-γ and as a putative mediator of proinflammatory T-T interactions in the intestinal mucosa. Taken together, these findings suggest LIGHT-herpesvirus entry mediator mediated signaling as an important immune regulatory mechanism in mucosal inflammatory responses.

The TNF superfamily cytokine, lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T cells (LIGHT; TNFSF14), can augment T cell responses inducing IFN-γ production and can drive pathological gut inflammation when expressed as a transgene in mouse T cells. LIGHT expression by human intestinal T cells suggests the possibility that LIGHT may play a key role in regulation of the mucosal immune system. A nonenzymatic method was developed for the isolation of T cells from the human lamina propria, permitting analysis of native cell surface protein expression. Cell surface LIGHT was constitutively expressed on mucosal T and NK cells and a subpopulation of gut-homing CD4+ T cells in the periphery. In addition, CD2-mediated stimulation induced efficient LIGHT expression on intestinal CD4+ T cells, but not on peripheral blood T cells, suggesting a gut-specific, Ag-independent mechanism for LIGHT induction. By contrast, herpesvirus entry mediator expression on gut T cells was unperturbed, implicating the transcriptional regulation of LIGHT as a mechanism modulating signaling activity in the gut. Quantitative analysis of LIGHT mRNA in a cohort of inflammatory bowel disease patients indicated elevated expression in biopsies from small bowel and from inflamed sites, implicating LIGHT as a mediator of mucosal inflammation.

The non-circulative, semi-persistent (NCSP) mode of insect vector-mediated plant virus transmission is shaped by biological, molecular and mechanical interactions that take place across a continuum of processes involved in virion acquisition, retention and inoculation. Our understanding of the interactive roles of virus, insect vector, and plant associated with NCSP transmission is still evolving. Mechanisms exist that determine where and how virion acquisition (from the plant) and retention (in the insect vector) are achieved, with both processes being mediated by strategies involving viral capsid proteins, in some cases aided by non-capsid proteins. By contrast, mechanisms underlying virion inoculation (to the plant) remain poorly understood. Here, we review the established paradigms as well as fresh perspectives on the mechanisms of NCSP transmission.

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