ESPN 53rd Annual Meeting

ESPN 2021


 
Decreased CD28 expression in memory CD4+ T cells in children awaiting kidney transplant is associated with increased expression of senescence markers
CHARLOTTE DUNETON 2 ROSHAN GEORGE 1 MANDY FORD 1 PAMELA WINTERBERG 1

1- EMORY UNIVERSITY, ATLANTA, USA
2- ROBERT DEBRé HOSPITAL, PARIS, FRANCE
 
Introduction:

Despite improved patient and graft outcomes with CD28-CD80/86 costimulation blockade, increased early acute rejection has hindered the widespread use of belatacept (CTLA-4Ig) for kidney transplant. Our group has previously reported lower pre-transplant frequencies of CD28+CD4+ effector memory helper T cells (CD4+TEM: CCR7- CD45RA-) with decreased functional capacity in adults that were subsequently free from early rejection on belatacept. We aimed to determine if a similar T cell phenotype is detectable in children awaiting kidney transplant.

Material and methods:

 We analyzed existing flow cytometry data of unstimulated blood cells collected from children on dialysis (n=30) or healthy children (n=18) and examined expression of markers of costimulation (CD28), senescence (CD57, PD1), activation (CD38) and cytotoxicity (Perforin, Granzyme B) on memory CD4+ T cells.

Results:

None of the children had CD28+CD4TEM frequencies as low as those we have previously observed in adults that were rejection-free on belatacept. However, 8 children on dialysis (27%) had CD28+CD4+TEM frequencies (median 92.56%, IQR 85.92-93,05) below the minimum value (96%) observed in healthy children (99.82%, 99.46-99.91; p<0.0001). Patients with this "stable-like" T cell phenotype had higher frequency of CD4+TEM cells bearing senescence markers (CD57+PD1+, p=0,011) and cytolytic effectors (Granzyme B, perforin, p=0,0004) but decreased activation markers (CD38+, p=0,003) compared to the rest of the dialysis patients.

Conclusions:

 Despite their young age and limited antigen experience, a subset of children on dialysis accumulate CD4+ TEM cells that have lost CD28 expression and bear markers suggestive of impaired function, a phenotype reminiscent of adults with decreased risk for early rejection on belatacept. The functional capacity of these cell populations in children needs further study.