Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance

Dendritic cells (DC) are inducers of immune responses par excellence. They also seem responsible for the induction of peripheral T cell tolerance. To investigate these opposite functions of DC, we generated a Cre/LoxP-based system that allows inducible antigen presentation by DC in vivo. This enables us to study the immunogical consequences of antigen presentation by resting versus mature DC without adoptively transferring DC and with physiological numbers of endogenous, naive responder T cells. We found that presentation of LCMV-derived CTL epitopes by resting DC resulted in antigen-specific tolerance, which could not be broken by subsequent infection with LCMV. On the other hand, antigen presentation by activated DC primed endogenous CTL to expand and to develop protective effector function

Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response

Radiotherapy induces DNA damage and cell death, but recent data suggest that concomitant immune stimulation is an integral part of the therapeutic action of ionizing radiation. It is poorly understood how radiotherapy supports tumor-specific immunity. Here we report that radiotherapy induced tumor cell death and transiently activated complement both in murine and human tumors. The local production of pro-inflammatory anaphylatoxins C3a and C5a was crucial to the tumor response to radiotherapy and concomitant stimulation of tumor-specific immunity. Dexamethasone, a drug frequently given during radiotherapy, limited complement activation and the anti-tumor effects of the immune system. Overall, our findings indicate that anaphylatoxins are key players in radiotherapy-induced tumor-specific immunity and the ensuing clinical responses