CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.

Area of Science:

• Immunology
• Transplantation immunology
• Cellular immunology

Background:

• Belatacept, a T cell costimulation blocker, prevents allograft rejection but is ineffective in some patients.
• Costimulation blockade-resistant rejection (CoBRR) is mediated by memory T cells in experimental models, but its human equivalent is unclear.
• Understanding the immune cell phenotypes associated with belatacept failure is crucial for improving transplant outcomes.

Purpose of the Study:

• To investigate the relationship between patient immune cell phenotypes and costimulation blockade-resistant rejection (CoBRR) in patients receiving belatacept or calcineurin inhibitors.
• To identify specific immune cell populations that may predict or contribute to acute rejection despite belatacept treatment.

Main Methods:

• Studied immune cell phenotypes in patients undergoing transplantation and receiving either belatacept or conventional immunosuppression.
• Utilized flow cytometry and transcriptional analysis to characterize T cell populations.
• Examined the presence of identified T cell populations in rejecting human kidney allografts.

Main Results:

• Identified a distinct population of CD57(+) PD1(-) CD4 T cells present before transplantation that correlated with CoBRR.
• Characterized these CD57(+) CD4 T cells as nonsenescent and cytolytic, expressing high levels of adhesion molecules and lacking CD28.
• Found these cells exhibited a transcriptional profile associated with allograft rejection and were present in rejecting kidney allografts.

Conclusions:

• CD57(+) CD4 T cells are implicated in clinical costimulation blockade-resistant rejection (CoBRR).
• This T cell population may serve as a predictive biomarker for identifying patients at higher risk of acute rejection when treated with belatacept.
• Further prospective validation is needed to confirm the clinical utility of CD57(+) CD4 T cells as a biomarker for belatacept therapy.