Regulatory T cells control strain specific resistance to Experimental Autoimmune Prostatitis

Maria L Breser,Ruben D Motrich,Jocelyne Demengeot,Virginia E Rivero,Andreia C Lino,Gloria J Godoy

doi:10.1038/srep33097

Abstract

Susceptibility to autoimmune diseases results from the encounter of a complex and long evolved genetic context with a no less complex and changing environment. Major actors in maintaining health are regulatory T cells (Treg) that primarily dampen a large subset of autoreactive lymphocytes escaping thymic negative selection. Here, we directly asked whether Treg participate in defining susceptibility and resistance to Experimental Autoimmune Prostatitis (EAP). We analyzed three common laboratory strains of mice presenting with different susceptibility to autoimmune prostatitis upon immunization with prostate proteins. The NOD, the C57BL/6 and the BALB/c mice that can be classified along a disease score ranging from severe, mild and to undetectable, respectively. Upon mild and transient depletion of Treg at the induction phase of EAP, each model showed an increment along this score, most remarkably with the BALB/c mice switching from a resistant to a susceptible phenotype. We further show that disease associates with the upregulation of CXCR3 expression on effector T cells, a process requiring IFNγ. Together with recent advances on environmental factors affecting Treg, these findings provide a likely cellular and molecular explanation to the recent rise in autoimmune diseases incidence.

Highlights

Susceptibility or resistance to autoimmune disorder has a clear genetic component in human and in mouse models[1]
In view of the natural dynamics and plasticity of Treg, these findings strengthen the notion that both genetic and environmental factors contribute to autoimmune disease susceptibility, the latter more explaining the recent rise in disease incidence. Both experimental autoimmune prostatitis (EAP) susceptible and resistant mice mount an immune response upon prostate antigen immunization
In all strains, immunization per se readily increased the number of CD4+ Foxp3+ cells when compared to steady state conditions (Fig. 1D). This increment was partially affected by prior anti-CD25 Ab treatment in NOD and BALB/c mice, but not in B6 animals, suggesting strain specific differences in the kinetics of Treg recovery/proliferation (Fig. 1D). Together these results indicate that all 3 strains do mount an immune response, limited by CD25+ regulatory cells, upon prostate antigens (PAg) immunization

Summary

Introduction

Susceptibility or resistance to autoimmune disorder has a clear genetic component in human and in mouse models[1]. Other models of induced autoimmunity rely on immunization with total protein extract of a given organ, multiplying the number of antigens in a single protocol and presumably enlarging the repertoire of effector cells, as is the case for experimental autoimmune prostatitis (EAP) where the immunogene is a protein extract of the whole prostate[8]. In these type of models too, the combination of strain and antigen mixture defines the outcome of immunization, and EAP is evident in NOD and C57BL/6 but undetected in BALB/c mice[9]. All mice strains mount antigen specific responses upon immunization, NOD mice develop a severe disease, C57BL/6 animals exhibit moderate prostate infiltration and BALB/c mice show no prostate tissue alterations[9,25]

Methods

Results

Conclusion