Balancing autoaggressive and protective T cell responses

Abstract

A finely orchestrated balance between activating and inhibitory signals is fundamental for the ability of the immune system to effectively attack and eliminate pathogenic microbes but to not react against self-antigens. Derangements of this balance underlie the pathogenesis of autoimmune diseases. Conversely, elucidating the mechanisms of this balance may provide rational strategies for manipulating it in order to enhance the efficacy of vaccines and tumor immunotherapy. One of the clearest illustrations of precise regulation is in the generation of effector and regulatory T cells. In order to analyze the mechanisms of this regulation, we have developed a transgenic mouse model in which a single population of T cells reacts against its known cognate antigen in vivo. Here we summarize our studies with this experimental model, illustrating the sequence of T cell responses that develop and attempting to dissect the stimuli that control these responses.

Figure 1. CD4 T-cell responses to a systemic antigen

The sequence of dominant responses of DO11 T-cells after transfer into sOva-Tg recipients are illustrated schematically. The signals required for the various responses and the known transcription factors involved are from various publications, and have not yet been established in the DO11 system.