Role of co-stimulatory molecules in macrophage regulation of T cell activation (147.3)

Abstract Murine peritoneal cavity (PerC) T cells from C57BL/6J mice respond poorly in vitro to CD3 ligation due to the high concentration of macrophages (Mϕs) found in this cell source. Mϕs suppressed T cell activation primarily by iNOS catabolism of arginine. Rather than costimulating T cell activation, CD28 ligation increased T cell suppression (“cosuppressed”). IFNγ is necessary for suppression as evidenced by the absence of co-suppression with IFNγRKO PerC Mϕs. To further investigate the co-suppression biology of this system, PerC cells from CD28KO, CD80KO, CD86KO, & CD80/86KO (B7KO) mice were studied. PerC T cells from CD28KO & B7KO mice had the lowest number of IFNγ-secreting cells (IFNγSC) & were the least susceptible to Mϕ-mediated suppression. CD86KO PerC cells included more IFNγSC & their T cells were more suppressed than CD80KO T cells. CD28 ligation costimulated B7KO PerC T cells yet cosuppressed both CD80KO & CD86KO PerC T cells, generating more IFNγSC in the latter. These data, consistent with the higher affinity of CD80 for CD28, suggest that CD80 might represent a biomarker for tumor progression, particularly when considered in conjunction with the density of Mϕs/myeloid-derived suppressor cells.