Mechanisms of macrophage suppression of splenic T cell proliferation
Pathology is often linked to inappropriate levels of immunogenicity or immunosuppression that occur within certain settings. The ability to augment or restrict macrophage suppressive function therefore offers the potential for therapeutic intervention. A detailed knowledge of the repertoire of macrophage suppressive mechanisms would be a pre-requisite for such manipulation. This study was developed to provide an in vitro macrophage/T cell co-culture model that could provide insights into suppressive events in vivo. Previous in vitro studies of macrophage anti-proliferative mechanisms have reported a complete dependence on nitric oxide production. This finding offers little scope for correlation with the majority of in vivo situations, where there is evidence that suppressive relationships are less straightforward. In contrast, the work described here showed that the overall picture is much more complex. Over a range of different types of experiment the suppressive role of NO was highly variable, and could even at times be irrelevant, as demonstrated by the use of iNOS-/- macrophages. PGE2 was shown to exert strain-dependent suppressive effects, but TGF-β did not appear to be involved. Additional suppressive mediators were clearly implicated but remained unidentified. To summarise, the results of this work provide evidence of the multiplicity, pleiotropy, redundancy and strain-dependence that may relate to macrophage mechanisms of T cell suppression. Inconsideration of investigations that are both described here and also indicated for future work, this model has previously undescribed potential to link in vitro findings with the highly complex interactions likely to be encountered in vivo.