Spleens were harvested in 1 (C) or 2 wpi (B, C) and cells were analyzed by movement cytometry in comparison to na?ve mice. Treg depletion improved the creation of virus-specific and virus-neutralizing antibodies and reduced FV viremia. Thus, in contrast to influenza infection, Tregs either directly or indirectly suppress B cells during mouse retroviral infection indicating that the ultimate effect of Tregs on B cell responses is specific to the particular infectious agent. Introduction Regulatory T cells (Tregs) are immunosuppressive CD4+ T cells that express the transcription factor Foxp3 and play a predominant role in immunological homeostasis and the prevention Istaroxime of autoimmune diseases . Tregs can also dampen immune responses to infectious agents (reviewed in ). Many studies have focused on effector T cells as targets of Treg suppression, but recent evidence shows that B cells and germinal center responses also fall under the control of Tregs [3C5] as a mechanism to prevent the production of autoantibodies [6C8]. Treg depletion studies have revealed a role for Istaroxime Tregs in preventing an outgrowth of non-antigen specific B cells in germinal centers . Istaroxime Further evidence for Treg suppression of B cells has been shown in recent immunization studies employing the experimental antigen NP-ovalbumin [9, 10]. In contrast to studies done using experimental antigens such as NP-KLH, Ova or sheep red blood cells, which showed Treg-mediated suppression of B cell/antibody responses, a study done Rabbit Polyclonal to Akt in mice infected with live influenza virus showed that depletion of Tregs severely Istaroxime reduced, rather than enhanced, B cell responses and antibody production . These studies suggested context dictates whether Tregs enhance or suppress the production of antibodies. They also illustrated that while studies using model antigens are very important for elucidating basic mechanisms of immunological responses, it is also essential to study live viral infections, which induce much more complex responses and may give surprising results. In this regard, we sought to determine the effect of Tregs on antibody responses to a mouse retroviral infection. In the current study we used mice infected with Friend virus (FV), a naturally occurring mouse retrovirus that causes acute infections that become chronic [12, 13]. FV infections induce the activation and proliferation of natural or thymus-derived tTregs, but does not induce the conversion of conventional T cells into Tregs . FV-induced Tregs have previously been demonstrated to suppress the function of both CD4+  and CD8+ T cells [16, 17]. FV infections were done in B6.FOXP3-DTR mice , which express the human diphtheria toxin (DT) receptor downstream and under transcriptional control of the FOXP3 locus. FOXP3 is a transcriptional factor that is required for Treg differentiation and function . Injection of DT into these mice specifically depletes Tregs . A role for Tregs in suppressing antiviral immune responses was originally shown in studies using the FV model , Istaroxime but until now Treg-mediated effects have focused on T cells [15, 20C22]. Treg-mediated influences on FV-specific antibody responses have not yet been investigated. The current results demonstrate potent suppression by Tregs on the development of specific antibody responses to acute retroviral infection. Materials and methods Mice Experiments were conducted using female B6.129(Cg)-cells following incubation with dilutions of plasma [23, 25]. The titer was defined as the dilution at which 50% of the input virus was neutralized..
- KY\02327 showed zero genetic toxicity within a bacterial change mutation assay (Maron & Ames, 1983) (Appendix?Desk?S3)
- CY designed the scholarly research, contributed towards the dialogue and edited the manuscript
- That is important if you want to better understand and predict chlamydia and transmission dynamics and evolution from the virus
- By keeping CD8+ T cell alloreactivity out, this CD4+ T cell-restricted model allows us to investigate the reciprocal interplay between Th1, Th17 and Treg cells in the context of transplantation