Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3⁺ T Cells

CXCR5⁺ T follicular helper (Tfh) cells are associated with aberrant autoantibody production in patients with antibody-mediated autoimmune diseases including lupus. Follicular regulatory T (Tfr) cells expressing CXCR5 and Bcl6 have been recently identified as a specialized subset of Foxp3+ regulatory T (Treg) cells that control germinal center reactions. In this study, we show that retroviral transduction of CXCR5 gene in Foxp3⁺ Treg cells induced a stable expression of functional CXCR5 on their surface. The Cxcr5-transduced Treg cells maintained the expression of Treg cell signature genes and the suppressive activity. The expression of CXCR5 as well as Foxp3 in the transduced Treg cells appeared to be stable in vivo in an adoptive transfer experiment. Moreover, Cxcr5-transduced Treg cells preferentially migrated toward the CXCL13 gradient, leading to an effective suppression of antibody production from B cells stimulated with Tfh cells. Therefore, our results demonstrate that enforced expression of CXCR5 onto Treg cells efficiently induces Tfr cell-like properties, which might be a promising cellular therapeutic approach for the treatment of antibody-mediated autoimmune diseases.

Blockade of STAT3 in T Cells Inhibits Germinal Center Reactions against Intranasal Allergens

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of TGF-β. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Co-transfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

Function and correlation of follicular helper T cells and B cells in alcohol abuse non-traumatic osteonecrosis of femoral head / 中国免疫学杂志

Objective:To examine the roles of follicular helper T(Tfh)cells,serum IL-21 and B cells in the pathogenesis of alcohol abuse non-traumatic osteonecrosis of the femoral head ( NONFH ) .Flow cytometry was used to measure the frequencies of peripheral blood inducible Tfh cells and B cells in alcohol abuse NONFH patients and healthy controls.The disease progression and the extent of femoral head collapse,the serum IL-21 were quantified.Methods: A significantly higher percentages of CD19+B cells(t=3.765,P=0.0005),CD86+CD19+B cells(t=5.506,P<0.0001),and CD95+CD19+B cells(t=4.152,P=0.0002) in patients than those in controls was found.The percentages of CD86+CD19+B cells were positively associated with the index of femoral head collapse in alcohol abuse NONFH(P<0.0001,r=0.536).Results: The frequencies of Tfh cells (t=7.611,P<0.0001),and IL-21+Tfh cells (t=5.281,P<0.0001) were higher than those in controls;The frequencies of Tfh cells were positively associated with the percentages of CD19+B cells(P=0.0002,r=0.455),IL-21+Tfh cells were positively associated with the percentages of CD86+CD19+B cells(P=0.0002,r=0.447).Conclusion: Tfh cells and B cells may participate in the pathogenesis of alcohol abuse NONFH,and increased CD86+CD19+B cells may be associated with the extent of femoral head collapse,the interaction of Tfh cells and B cells may have an im-portant role in pathogenesis of alcohol abuse NONFH.

Characteristics of tfh cells in the peripheral blood in recipients of liver allograft: A pilot study / 解放军医学杂志

Objective To determine the expression characteristics of peripheral blood follicular helper T cells (Tfh) and their molecules during pre- and post-transplantation period in liver transplant patients to explore the role of Tfh in alloreactive response after liver transplantation. Methods Twenty liver transplant (LT) patients and 20 healthy individuals as control were enrolled in this study. Thirteen LT patients with stable liver function were included for cross-sectional study. Another seven LT patients with complete clinical data were included for follow-up study. The frequencies of Tfh cells were examined by flow cytometry. For the seven patients, Tfh cells and level of alanine aminotransferase (ALT) were monitored dynamically for one month after LT. Results The frequencies of CD4+CXCR5+Tfh and CD4+CXCR5+PD-1+ cells in peripheral blood increased significantly after liver transplantation as compared with those before liver transplantation (P<0.05). In addition, the frequencies of CD4+CXCR5+ICOS+ cells showed a rising trend, but no statistical difference. In early follow-up period it was found that the frequencies of CD4+CXCR5+ Tfh obviously increased after liver transplantation in patients with stable liver function, and reached the peak value after one week and then decreased. The AL level also decreased when reaching peak 10 days after surgery. Interestingly, the frequencies of CD4+CXCR5+ Tfh in one patient with acute rejection after liver transplantation showed the same trend with ALT levels changes. Furthermore, the frequencies of CD4+CXCR5+Tfh, CD4+CXCR5+PD-1+ and CD4+CXCR5+ICOS+ cells in stable liver function group were higher than those in the healthy control group (P<0.05). Conclusion The CD4+CXCR5+Tfh cells in peripheral blood will be upregulated in liver transplant patients, which indicates that the Tfh maybe involved in liver alloreactive response.