Tolerant T cells display impaired trafficking ability

Abstract

Based on our previous observation that anergic T lymphocytes lose their migratory ability in vitro, we have proposed that anergic T cells are retained in the site where they have been generated to exert their regulatory function. In this study we have analyzed T lymphocyte trafficking and motility following the induction of tolerance in vivo. In a model of non-deletional negative vaccination to xenoantigens in which dendritic cells (DC) localize to specific lymphoid sites depending on the route of administration, tolerant T cells remained localized in the lymph nodes colonized by tolerogenic DC, while primed T cells could traffic efficiently. Using an oral tolerance model that enables the 'tracking' of ovalbumin-specific TCR-transgenic T cells, we confirmed that T cells lose the ability to migrate through syngeneic endothelial cell monolayers following tolerance induction in vivo. Finally, we show that tolerant T cells (both in vitro and ex vivo) can inhibit migration of responsive T cells in an antigen-independent manner. Thus, hyporesponsive T cells localize at the site of tolerance induction in vivo, where they exert their anti-inflammatory properties. In physiological terms, this effect is likely to render immunoregulation a more efficient and controllable event.

Effect of recombinant Lactococcus lactis producing myelin peptides on neuroimmunological changes in rats with experimental allergic encephalomyelitis

“…Dendritic cells in the GALT present the gut-derived antigens to naïve T cells in Peyer's patches, what results in differentiation of T cells into regulatory T cells (Tregs) producing IL-10 and TGF-β, or internalization of TCR leading to anergy. Thus, orally administered fragments of myelin peptides induce, depending on the antigen dose, active suppression (inhibiting of Th1-dependent immunoresponse) or anergy/clonal deletion of responsive T lymphocytes (both Th1 and Th2) in the mucosal immune system [4,27,40]. Anergic T cells are not able to migrate from the site of tolerance induction, and remaining in the GALT produce anti-inflammatory cytokines.…”

Mannosylated lipopetides as model vaccines for targeting the mannose receptor

“…activation. This has been reported by Mirenda et al [333]. They reported that partial T cell activation can cause T cell unresponsiveness (anergic T cells) due to the defects caused on the T cells migratory ability [333,334].…”

“…It is also argued that this epitope also bears at least one B cell epitope (323)(324)(325)(326)(327)(328)(329)(330)(331)(332)(333)(334)(335)(336)(337)(338)(339), however, there is only one study that has mentioned the presence of the B cell epitope [327]. In a study by Sun et al, it was shown that 50% of the B cell response generated by the OVA protein was antibody specific to the OVA323-339 epitope [327].…”

“…In a study by Sun et al, it was shown that 50% of the B cell response generated by the OVA protein was antibody specific to the OVA323-339 epitope [327]. As the vaccine structures (G1-6) contain the CD4 epitope (OVA [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339], the in vivo ability of vaccine structures (G1-9) for a T cell activation proliferation was assessed. Here, OT-II proliferating cells are considered to be activated when T cells expressing CD45.2 increase in percentage over the total parental CD4 + T cells [329].…”

“…The OVA protein naturally exists as a glycoprotein, however, it was discovered that the OVA [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339] and OVA 1-10 sequences of the OVA protein bore a B cell epitope that was capable of inducing a T cell response. This discovery was obtained by T cell mediated IgE responses that were observed against an assumed B cell epitope inside OVA323-339 and OVA1-10 peptides [185].…”