Mouse Anti-Human MHC class II (HLA-DR) monoclonal antibody, clone L234

Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) subsets compared with healthy controls (HCs). BTLA expression was similarly high in untreated TB, TB relapse, and sputum-bacillus positive TB, but anti-TB therapy reduced TB-driven increases in frequencies of BTLA(+) DCs. BTLA(+) DCs in active TB showed decreased expression of the DC maturation marker CD83, with an increased expression of CCR7 in mDCs. BTLA(+) DCs in active TB displayed a decreased ability to express HLA-DR and to uptake foreign antigen, with a reduced expression of the co-stimulatory molecule CD80, but not CD86. Functionally, BTLA(+) DCs in active TB showed a decreased production of IL-12 and IFN-alpha as well as a reduced ability to stimulate allogeneic T-cell proliferative responses. BTLA(+) mDCs produced larger amounts of IL-4 and TGF-beta than BTLA(-) mDCs in both HCs and APT patients. BTLA(+) DCs from active TB patients showed a reduced ability to stimulate Mtb antigen-driven Th17 and Th22 polarizations as compared to those from HCs. Conversely, these BTLA(+) DCs more readily promoted the differentiation of T regulatory cells (Treg) and Th2 than those from HCs. These findings suggest that TB-driven BTLA expression in DCs impairs the expression of functional DC surrogate markers and suppress the ability of DCs to induce anti-TB Th17 and Th22 response while promoting Th2 and Foxp3(+) Tregs.

Chronic hepatitis B virus (CHBV) infection is a major cause of liver diseases. Mucosal-associated invariant T (MAIT) cells are important for antiviral immunity in the liver, but the distinction between intrasinusoidal and peripheral MAIT cells in patients with CHBV infections remains unclear. PBMCs were obtained from patients with CHBV infections (n = 29) and age-matched controls (n = 46). Liver-associated mononuclear cells (LMCs) were collected from healthy donors (n = 29) and explanted livers (n = 19) from patients and used for phenotypic, functional and TCR diversity analyses. The percentages of both peripheral and intrasinusoidal MAIT cells were significantly reduced in the CHBV infection group compared to the control group. Peripheral MAIT cells from CHBV-infected patients expressed higher levels of HLA-DR, CD69, CD38 and PD-1 than those of controls. We also confirmed that peripheral MAIT cells in HBV patients had elevated expression T-cell exhaustion genes. Except for a difference in the level of PD-1, no differences were observed between the liver MAIT cells of the two groups. The production of IFN-alpha in peripheral MAIT cells of CHBV infection patients was lower than in control patients, but no such difference was observed in liver MAIT cells. Additionally, a distinct TCR signature was found in CHBV patients. Hence, we found distinct activities and functions in liver and peripheral MAIT cells of patients with CHBV infections.