Kidney Week

Abstract: PO2346

Decreased CD28 Expression in Memory CD4⁺ T Cells in Children Awaiting Kidney Transplant Is Associated with Increased Expression of Senescence Markers

Session Information

• 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

Authors

• Duneton, Charlotte, Emory University, Atlanta, Georgia, United States

Charlotte Duneton,

• George, Roshan P., Emory University, Atlanta, Georgia, United States

Roshan P. George,

• Ford, Mandy L., Emory University, Atlanta, Georgia, United States

Mandy L. Ford,

• Winterberg, Pamela D., Emory University, Atlanta, Georgia, United States

Pamela D. Winterberg,

Background

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⁺T_EM 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.

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⁺CD4⁺ T_EM 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⁺T_EM frequencies below the minimum value observed in healthy children (Fig1A-B). Patients with this "stable-like" T cell phenotype had higher frequency of CD4⁺T_EM cells bearing senescence markers (CD57⁺PD1⁺ Fig 1C) and cytolytic effectors (Granzyme B, Perforin, Fig 1D) but decreased activation markers (CD38⁺ Fig 1E).

Conclusion

Despite their young age and limited antigen experience, a subset of children on dialysis accumulate CD4⁺ T_EM 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.

Funding

• NIDDK Support