Decreased CD28 Expression in Memory CD4<sup>+</sup> T Cells in Children Awaiting Kidney Transplant Is Associated with Increased Expression of Senescence Markers
October 22, 2020 | 10:00 AM - 12:00 PM
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Decreased CD28 Expression in Memory CD4+ T Cells in Children Awaiting Kidney Transplant Is Associated with Increased Expression of Senescence Markers
- Pediatric Nephrology: Glomerular Disease and Transplantation
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
- Duneton, Charlotte, Emory University, Atlanta, Georgia, United States
- George, Roshan P., Emory University, Atlanta, Georgia, United States
- Ford, Mandy L., Emory University, Atlanta, Georgia, United States
- Winterberg, Pamela D., Emory University, Atlanta, Georgia, United States
Roshan P. George,
Mandy L. Ford,
Pamela D. Winterberg,
Despite improved patient and graft outcomes with CD28-CD80/86 costimulation blockade, increased early acute rejection has hindered the widespread use of CTLA-4Ig (belatacept) for kidney transplant. Our group has previously reported lower pre-transplant frequencies of CD28+ 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.
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.
None of the children had CD28+CD4+ TEM 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 below the minimum value observed in healthy children (Fig1A-B). Patients with this "stable-like" T cell phenotype had higher frequency of CD4+TEM cells bearing senescence markers (CD57+PD1+ Fig 1C) and cytolytic effectors (Granzyme B, Perforin, Fig 1D) but decreased activation markers (CD38+ Fig 1E).
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.
- NIDDK Support