Frontline Science: PECAM-1 (CD31) expression in naïve and memory, but not acutely activated, CD8+ T cells

Abstract

Inhibitory cell surface proteins on T cells are often dynamically regulated, which contributes to their physiologic function. PECAM-1 (CD31) is an inhibitory receptor that facilitates TGF-β-mediated suppression of T cell activity. It is well established in CD4 T cells that PECAM-1 is expressed in naïve recent thymic emigrants, but is down-regulated after acute T cell activation and absent from memory cells. The extent to which PECAM-1 expression is similarly regulated in CD8 T cells is much less well characterized. We evaluated T cells recovered from mice after infection with a model intracellular pathogen and determined that, in CD8 T cells, PECAM-1 expression was strongly down-regulated during acute infection but re-expressed to intermediate levels in memory cells. Down-regulation of PECAM-1 expression in CD8 T cells was transcriptionally regulated and affected by the strength and nature of TCR signaling. PECAM-1 was also detected on the surface of human activated/memory CD8 , but not CD4 T cells. These data demonstrate that PECAM-1 expression is dynamically regulated, albeit differently, in both CD4 and CD8 T cells. Furthermore, unlike memory CD4 T cells, memory CD8 T cells retain PECAM-1 expression and have the potential to be modulated by this inhibitory receptor.

Neonatal influenza-specific effector CTLs retain elevated CD31 levels at the site of infection and have decreased IFN-γ production

“…Recently Newman and colleagues reported that transcriptional down‐regulation, and not extracellular domain cleavage, is responsible for decreased levels of expression of CD31 in activated effector CTLs . In agreement with this, we found adult CD31 + effector CTLs produce very little CD31 transcript.…”

“…Given the increase in CD31 + CTLs in the lungs of neonatal animals during influenza virus infection we questioned if this was simply due to the large thymic output at this young age, or if there was an ongoing transcriptional regulation of CD31 ( Pecam1 ). There is conflicting data whether upon activation, CD31 is proteolytically cleaved from the surface of CD8 + T cells or transcriptionally regulated . First, baseline transcription of naïve CD31 + and CD31 − CTLs was determined by sorting these CTLs from the lungs of neonatal and adult animals (Fig.…”

“…There is conflicting data whether upon activation, CD31 is proteolytically cleaved from the surface of CD8 + T cells or transcriptionally regulated. 20,21 First, baseline transcription of naïve CD31 + and CD31 − CTLs was determined by sorting these CTLs from the lungs of neonatal and adult animals ( Fig. 4C).…”

Dissecting the defects in the neonatal CD8+ T-cell response

“…In support of a differential regulation of CD31 expression between neonates and adult mice, CD8 + T cells expressing a transgenic TCR specific for the ova peptide SIINFEKL(OT‐I CD8 + T cells) were injected into hosts immediately prior to infection with ova‐peptide expressing L. monocytogenes (Lm‐ova). At 8 and 15 days postinfection, OT‐I CD8 + T cells were sorted and found to have a significant reduction in Pecam‐1 transcripts . Interestingly, CD31 can colocalize with the TGFβ receptor on the cell surface to enhance the suppressive effects of TGFβ .…”

“…At 8 and 15 days postinfection, OT-I CD8 + T cells were sorted and found to have a significant reduction in Pecam-1 transcripts. 87 Interestingly, CD31 can colocalize with the TGF receptor on the cell surface to enhance the suppressive effects of TGF . 88 Given that TGF levels are elevated in multiple neonatal infection models, it is interesting to speculate that neonatal CTLs would be exquisitely sensitive to TGF /CD31-mediated suppression.…”