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Antigen-specific Regulatory T Cells (antigen-specific + regulatory_t_cell)
Selected AbstractsVaccines modulating lipoprotein autoimmunity as a possible future therapy for cardiovascular diseaseJOURNAL OF INTERNAL MEDICINE, Issue 3 2009J. Nilsson Abstract. Current strategies for prevention of cardiovascular disease focus on risk factor intervention. Although these have been proven both safe and effective results from randomized clinical trials suggest that it is difficult to achieve relative risk reductions exceeding 40% with this approach. To further improve efficacy future therapies must aim at targeting the actual disease process in the arterial wall. Emerging evidence have identified an important role of the immune system in atherosclerosis and suggest that modulation of autoimmune responses against oxidized LDL and other antigens in the atherosclerotic plaque represent one possible new approach to disease prevention. Oxidized LDL is targeted by both antibody-mediated and cellular immune responses and as much as 10% of the T cells in atherosclerotic plaques are oxidized LDL-specific. Immune activation in the atherosclerotic plaque is primarily of the pro-inflammatory Th1-type and inhibition Th1 immunity reduces atherosclerosis in experimental animals. Atherosclerosis vaccines based on antigens derived from LDL have been developed to modulate these processes. Their mechanisms of action remain to be full characterized but may involve expression of protective antibodies that facilitate the removal of oxidized LDL and antigen-specific regulatory T cells that counteract Th1 autoimmunity against oxidized LDL. In this review we will discuss the possibilities and challenges encountering the translation of immune-modulatory therapy for atherosclerosis from the experimental stage into the clinic. [source] Vaccination against hepatitis B in liver transplant recipients: Pilot analysis of cellular immune response shows evidence of HBsAg-specific regulatory T cellsLIVER TRANSPLANTATION, Issue 3 2007Tanja Bauer After liver transplantation for hepatitis-B-related diseases, patients currently receive lifelong treatment with hepatitis B immunoglobulin to prevent endogenous reinfection with hepatitis B virus (HBV). Active immunization with hepatitis B vaccine would be a preferable alternative; however, most attempts to immunize these patients with standard vaccine have failed. A recent study with a new adjuvanted hepatitis B vaccine was exceptionally successful, leading to a high-titered long-lasting antibody response in 80% of all vaccinees. To identify the immunological mechanisms behind these unexpected results, the successfully vaccinated participants were tested for hepatitis B surface antigen (HBsAg)-specific T and B cells, and their cellular responses to revaccination with conventional vaccine were studied. HBsAg-specific CD4+ T lymphocytes could be detected in 13 of 16 patients after immunization with the new vaccine. Unexpectedly, these T cells produced almost exclusively interleukin (IL)-10 and had a CD4+/CD25+ phenotype. They were functionally active, suppressing cytokine secretion in HBsAg-specific (Th1) cells, thus representing antigen-specific regulatory T cells (TReg). Following a booster dose with conventional vaccine 22-31 months after completion of the initial vaccination series, the T-cell pattern in the revaccinated individuals changed substantially: 7 days after revaccination 9 of 11 individuals showed a switch to a Th1-type immune response with HBsAg-specific T cells secreting IL-2, interferon gamma and tumor necrosis factor alpha as observed in healthy controls. Four weeks after the booster, 4 patients still showed a Th1-type cytokine pattern, whereas in 5 patients only IL-10-secreting cells were detectable. After 1 year, in 3 of 4 revaccinated individuals only IL-10-secreting cells could be found, whereas the specific T cells of the fourth patient still showed a Th1-type of response. HBsAg-specific TReg cells could be demonstrated in HBV-positive liver transplant recipients successfully immunized with a new adjuvanted vaccine. Revaccination led to immediate disappearance of the these cells and the appearance of HBsAg-specific T cells with a Th1-type cytokine profile, which in most cases were replaced by the IL-10-secreting regulatory cells during the following months. The specific induction of TReg cells could contribute to the poor response of liver transplant recipients to conventional vaccine. In conclusion,, for successful vaccination of these patients, a vaccine with a strong inhibitory effect on TReg cells would be desirable. Liver Transpl 13:434,442, 2007. © 2007 AASLD. [source] DNA Damage, Apoptosis and Langerhans Cells,Activators of UV-induced Immune Tolerance,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2008Laura Timares Solar UVR is highly mutagenic but is only partially absorbed by the outer stratum corneum of the epidermis. UVR can penetrate into the deeper layers of the epidermis, depending on melanin content, where it induces DNA damage and apoptosis in epidermal cells, including those in the germinative basal layer. The cellular decision to initiate either cellular repair or undergo apoptosis has evolved to balance the acute need to maintain skin barrier function with the long-term risk of retaining precancerous cells. Langerhans cells (LCs) are positioned suprabasally, where they may sense UV damage directly, or indirectly through recognition of apoptotic vesicles and soluble mediators derived from surrounding keratinocytes. Apoptotic vesicles will contain UV-induced altered proteins that may be presented to the immune system as foreign. The observation that UVR induces immune tolerance to skin-associated antigens suggests that this photodamage response has evolved to preserve the skin barrier by protecting it from autoimmune attack. LC involvement in this process is not clear and controversial. We will highlight some basic concepts of photobiology and review recent advances pertaining to UV-induced DNA damage, apoptosis regulation, novel immunomodulatory mechanisms and the role of LCs in generating antigen-specific regulatory T cells. [source] FK506 as an adjuvant of tolerogenic DNA vaccination for the prevention of experimental autoimmune encephalomyelitisTHE JOURNAL OF GENE MEDICINE, Issue 11 2009Youmin Kang Abstract Background DNA vaccination is a strategy that has been developed primarily to elicit protective immunity against infection and cancer. Methods DNA vaccine was used, in conjunction with an immunosuppressant, to tolerize harmful autoimmunity. Results Immunization of C57BL/6 mice with MOG35,55, a myelin oligodendrocyte glycoprotein-derived peptide, and FK506 (Tacrolimus) as a tolerogenic adjuvant stimulated regulatory dendritic cells, induced antigen-specific regulatory T cells (Treg), and protected the animals from subsequent induction of experimental autoimmune encephalomyelitis (EAE). After EAE induction, there were fewer lymphocytes, including fewer T helper 17 cells, and more Treg infiltrating the spinal cord in the immunized mice compared to in control mice. Furthermore, at the peak of the EAE manifestation, CD4 T cells in the immunized mice showed decreased expression of interferon-, and interleukin (IL)-17, but not IL-4, in treated mice. Conclusions DNA vaccination, when applied with an immunosuppressant as adjuvant, can induce antigen-specific tolerance and prevent autoimmune disease. Copyright © 2009 John Wiley & Sons, Ltd. [source] Tolerogenic Dendritic Cells: All Present and Correct?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010A. W. Thomson Although well-recognized for their sentinel role and, when activated, their immunostimulatory function, bone marrow-derived dendritic cells (DC) possess inherent tolerogenic (tol) ability. Under quiescent conditions, these cells maintain central and peripheral self tolerance. When appropriately conditioned, in vitro or in vivo, they inhibit innate and adaptive immunity to foreign antigens, including memory T-cell responses. This suppressive function is mediated by various mechanisms, including the expansion and induction of antigen-specific regulatory T cells. Extensive experience in rodent models and recent work in nonhuman primates, indicate the potential of pharmacologically-modified, tol DC (tolDC) to regulate alloimmunity in vivo and to promote lasting, alloantigen-specific T-cell unresponsiveness and transplant survival. While there are many questions yet to be addressed concerning the functional biology of tolDC in humans, these cells offer considerable potential as natural, safe and antigen-specific regulators for long-term control of the outcome of organ and hematopoietic cell transplantation. This minireview surveys recent findings that enhance understanding of the functional biology and therapeutic application of tolDC, with special reference to transplantation. [source] | |||||||||||||