[show abstract][hide abstract] ABSTRACT: Mesenchymal stem cells (MSCs) are multi-potent progenitor cells that are isolated from the bone marrow and several adult organs and tissues. These cells possess remarkable immunosuppressive properties and can inhibit the proliferation and function of the major immune cell populations, including T cells, B cells and natural killer (NK) cells; modulate the activities of dendritic cells (DCs); and induce regulatory T cells both in vivo and in vitro. These unique properties make MSCs ideal candidates for clinical application as immunosuppressants. The immunomodulatory effect of MSCs is mediated by a non-specific anti-proliferative action of these cells, which is dependent on cell-cell contact or secreted soluble factors such as indoleamine 2,3-dioxygenase (IDO), prostaglandin E(2) (PGE(2) ), nitric oxide (NO), histocompatibility leucocyte antigen-G (HLA-G), transforming growth factor (TGF)-β, interferon (IFN)-γ and interleukin (IL)-1β. Considerable progress has been obtained in preclinical studies on MSCs, including those on their ability to activate allogeneic cells. This review examines the current understanding of the immunomodulatory properties of MSCs and its therapeutic implication for immune-mediated diseases and transplant rejection.
[show abstract][hide abstract] ABSTRACT: HBs antigen (HBsAg)183-191 (FLLTRILTI, R187 peptide) is a dominant human leucocyte antigen-A2 (HLA-A2)-restricted epitope associated with hepatitis B virus (HBV) infection in Caucasian populations. However, its prevalence is poorly understood in China, where there is a high incidence of HBV infection. In this report, we sequenced the region of HBsAg derived from 103 Chinese patients. Approximately 16.5% of the patients bore a mutant HBsAg183-191 epitope in which the original arginine (R187) was substituted with a lysine (K187 mutant peptide). Importantly, K187 still bound to HLA-A2 with high affinity, and elicited specific cytotoxic T lymphocyte (CTL) responses in HLA-A2/K(b) transgenic mice. K187-specific CTLs were also generated successfully in acute hepatitis B (AHB) patients, indicating that this mutant epitope is processed and presented effectively. Our findings show that R187-specific CTLs can cross-react with the K187 peptide. These findings reveal that K187 still has the property of an HLA-A2 restricted epitope, and elicits a protective anti-HBV CTL response in humans.
[show abstract][hide abstract] ABSTRACT: To investigate whether hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells (MoDC) could mount a T cell response in hepatocellular carcinoma (HCC) patients associated with chronic HBV infection, peripheral blood mononuclear cells (PBMCs) from 36 HBV-associated HCC patients were induced into MoDC and pulsed with hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg), alone and in combination. Co-stimulatory molecules CD80, CD86 and CD40, as well as human leucocyte antigens D-related (HLA-DR) were found to express at the highest level on MoDC pulsed with HBcAg or HBsAg + HBcAg, at a median level on MoDC pulsed with HBcAg or HBsAg alone, and at the lowest level on non-antigen-pulsed MoDC. Interleukin (IL)-10 and IL-12 cytokines were released by antigen-pulsed MoDC at increased levels in the order: no-antigen < HBsAg < HBcAg < HBcAg + HBsAg. MoDC pulsed with HBcAg or HBsAg + HBcAg also had the strongest ability to stimulate autologous T cell proliferation and intracellular interferon (IFN)-gamma production. HBcAg- or HBsAg + HBcAg-pulsed MoDC could also induce HBV core peptide-specific CD8(+) T cell proliferation determined by tetramer staining. In addition, the antigen-pulsed MoDC were found to have a stronger capacity to produce IL-12 and induce T cell response in vitro for patients with higher alanine transaminase (ALT) levels than those with lower ALT levels, indicating that antigen pulse could substantially reverse the impaired function of MoDC in primary HCC patients with active chronic hepatitis B. In conclusion, HBV antigen-pulsed MoDC from HCC patients with chronic hepatitis B could induce HBV-specific T cell response in vitro.