An excellent study by Japanese scientists in @sciencemagazine reveals how co-#stimulatory molecule #CD80 sequestered co-#inhibitory molecule #PDL1 on the same DC's surface and thus promotes #Tcell #activation. #immunology #tolerance #Immunotherapy https://t.co/RcArRXV9XT— David Usharauli (@3DiMMUNE) April 23, 2019
1. Initially, the authors made an #observation that unlike #macrophages #dendritic cells did not stain with soluble #PD1 molecule even though DCs expressed high levels of #PDL1 or #PDL2 (PD1 ligands). However, it was noted that DCs expressed a higher level of #CD80 too. pic.twitter.com/hH1CbYxt7L— David Usharauli (@3DiMMUNE) April 23, 2019
3. Co-expression of #PDL1 with #CD80 [but not with CD86 or PDL2 with CD80 or another co-#stimulatory molecule CD86], on the same cell surface had a #functional consequence for OVA-specific T cell activation. It allowed more vigorous #activation and IL-2 production. pic.twitter.com/X0miudAspA— David Usharauli (@3DiMMUNE) April 23, 2019
5. Here too, the combination of #PDL1 and #CD80 molecules that cannot interact with each other allowed more vigorous #inhibition of IL-2 production by T cells. #Mechanistically, it showed that 'liberated' PDL1 on DCs cross-interacts with PD1 on T cell and #inhibits it. pic.twitter.com/YxM6oskg3q— David Usharauli (@3DiMMUNE) April 23, 2019
7. Similarly, mice expressing mutant PDL1 or CD80 molecules showed reduced inflammation in the brain [in #EAE #model] after priming with brain-specific antigens though the effect seems to be minimal. pic.twitter.com/P2fyIusL1M— David Usharauli (@3DiMMUNE) April 23, 2019
It indicates PDL1 #sequestration by CD80 on DCs is not a major path that controls immunity in #physiological condition. The authors did not show if it undermines protection against #pathogens or #tolerance to gut #commensals.— David Usharauli (@3DiMMUNE) April 23, 2019
