Prolonged acceptance of skin grafts induced by B cells places regulatory T cells on the histopathology scene.

The participation of regulatory T (Treg) cells in B cell-induced T cell tolerance has been claimed in different models. In skin grafts, naive B cells were shown to induce graft tolerance. However, neither the contribution of Treg cells to B cell-induced skin tolerance nor their contribution to the histopathological diagnosis of graft acceptance has been addressed. Here, using male C57BL/6 naive B cells to tolerize female animals, we show that skin graft tolerance is dependent on CD25+ Treg cell activity and independent of B cell-derived IL-10. In fact, B cells from IL-10-deficient mice were able to induce skin graft tolerance while Treg depletion of the host inhibited 100% graft survival. We questioned how Treg cell-mediated tolerance would impact on histopathology. B cell-tolerized skin grafts showed pathological scores as high as a rejected skin from naive, non-tolerized mice due to loss of skin appendages, reduced keratinization and mononuclear cell infiltrate. However, in tolerized mice, 40% of graft infiltrating CD4+ cells were FoxP3+ Treg cells with a high Treg:Teff (effector T cell) ratio (6:1) as compared to non-tolerized mice where Tregs comprise less than 8% of total infiltrating CD4 cells with a Treg:Teff ratio below 1:1. These results render Treg cells an obligatory target for histopathological studies on tissue rejection that may help to diagnose and predict the outcome of a transplanted organ.

Anti-IL-5 immunomodulates the effect of Staphylococcus aureus enterotoxin on T cell response in nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a T helper-2 (Th2) inflammatory disease with considerable impact on the quality of life. Staphylococcus aureus enterotoxins (SAEs) can induce and/or amplify inflammation. In this study, we investigated the immunomodulatory effect of SAEs on cytokine production by T cell obtained from nasal polyps (NPs) and examined whether neutralizing interleukin 5 (IL-5) can reverse the immunological effect mediated by those toxins. METHODS: NP tissues were obtained from all patients who underwent endoscopic sinus surgery for CRSwNP. NP cells were isolated and stimulated in vitro with SAEs in the presence or absence of anti-IL-5. Flow cytometry (FACS) analyses were performed to measure specific T lymphocyte cytokine production. RESULTS: Seventeen patients (mean age 48 years) were enrolled. SAEs significantly increased the IL-4, IL-5 (Th2) and interferon (INF)-γ (Th1) cytokines released from T lymphocytes of NPs. The addition of anti-IL-5 suppressed IL-4 and INF-γ release, which was most evident on NP tissue with high basal levels of IL-5. CONCLUSIONS: Neutralizing IL-5 is a potential therapeutic modality in patients with NPs, the effect of which is dependent on IL-5 levels.