Effectiveness of soluble CTLA-4-Fc in the inhibition of bone marrow T-cell activation in context of indoleamine 2.3-dioxygenase (IDO) and CD4+Foxp3+ Treg induction

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease with systemic inflammation finally resulting in damaged joints. One of the RA development models suggests bone marrow (BM) as a place of inflammation development further leading to disease progression. We aimed to investigate the potential of CTLA-4-Fc molecule in inducing tolerogenic milieu in BM measured as indoleamine 2,3-dioxygenase (IDO) expression, CD4 METHODS: Bone marrow mononuclear cells (BMMC) were stimulated by pro-inflammatory cytokines and CTLA-4-Fc. Next IDO expression, CD4 RESULTS: We found that CTLA-4-Fc and IFN-γ stimulation results in IDO production by BMMC. CTLA-4-Fc induced tryptophan catabolism can inhibit mitogen-induced CD4 CONCLUSION: This study sheds light on some immunosuppression aspects present or induced in BM. The potential of IDO-mediated pathways were confirmed in the periphery, what may represent the promising candidates for therapeutic strategies in RA

Virus-Like Particles: Models for Assembly Studies and Foreign Epitope Carriers

Virus-like particles (VLPs), formed by the structural elements of viruses, have received considerable attention over the past two decades. The number of reports on newly obtained VLPs has grown proportionally with the systems developed for the expression of these particles. When expressed in a suitable heterologous system, viral structural proteins involved in capsid or envelope formation often self-assemble into VLPs in the absence of other viral components usually required for virus assembly, such as multiple structural or nonstructural proteins and viral genomes. Protein–protein interactions in VLPs are relatively strong and can result in the formation of stable structures. Several experiments have been reported that may help answer questions regarding the requirements for VLP formation. Knowledge on the assembly process of VLPs is crucial to define the usefulness of such particles for the presentation of their own or foreign epitopes as carriers for transiently expressed proteins as a means of vaccine production. The aim of the present chapter is to outline recent achievements in two important fields of research brought about by the availability of VLPs produced in a foreign host. These are (1) the requirements for VLP assembly and (2) the use of VLPs as carriers for foreign epitopes. To date, reviews in these areas have mainly focused on results obtained with a specific virus genus or family of viruses (1, 2, 3, 4 and 5) and the reader is advised to refer to these reviews for complementary information. Virus-like particles (VLPs), formed by the structural elements of viruses, have received considerable attention over the past two decades. The number of reports on newly obtained VLPs has grown proportionally with the systems developed for the expression of these particles. When expressed in a suitable heterologous system, viral structural proteins involved in capsid or envelope formation often self-assemble into VLPs in the absence of other viral components usually required for virus assembly, such as multiple structural or nonstructural proteins and viral genomes. Protein–protein interactions in VLPs are relatively strong and can result in the formation of stable structures. Several experiments have been reported that may help answer questions regarding the requirements for VLP formation. Knowledge on the assembly process of VLPs is crucial to define the usefulness of such particles for the presentation of their own or foreign epitopes as carriers for transiently expressed proteins as a means of vaccine production. The aim of the present chapter is to outline recent achievements in two important fields of research brought about by the availability of VLPs produced in a foreign host. These are (1) the requirements for VLP assembly and (2) the use of VLPs as carriers for foreign epitopes. To date, reviews in these areas have mainly focused on results obtained with a specific virus genus or family of viruses (1, 2, 3, 4 and 5) and the reader is advised to refer to these reviews for complementary information. Virus-like particles (VLPs), formed by the structural elements of viruses, have received considerable attention over the past two decades. The number of reports on newly obtained VLPs has grown proportionally with the systems developed for the expression of these particles. When expressed in a suitable heterologous system, viral structural proteins involved in capsid or envelope formation often self-assemble into VLPs in the absence of other viral components usually required for virus assembly, such as multiple structural or nonstructural proteins and viral genomes. Protein–protein interactions in VLPs are relatively strong and can result in the formation of stable structures. Several experiments have been reported that may help answer questions regarding the requirements for VLP formation. Knowledge on the assembly process of VLPs is crucial to define the usefulness of such particles for the presentation of their own or foreign epitopes as carriers for transiently expressed proteins as a means of vaccine production. The aim of the present chapter is to outline recent achievements in two important fields of research brought about by the availability of VLPs produced in a foreign host. These are (1) the requirements for VLP assembly and (2) the use of VLPs as carriers for foreign epitopes. To date, reviews in these areas have mainly focused on results obtained with a specific virus genus or family of viruses (1, 2, 3, 4 and 5) and the reader is advised to refer to these reviews for complementary information

Virus-Like Particles: Models for Assembly Studies and Foreign Epitope Carriers

Virus-Like Particles: Models for Assembly Studies and Foreign Epitope Carrier