Purpose: This investigator-initiated study examines the impact of belatacept on T cell immune phenotype and function.

Methods: 14 patients who had completed the study protocol were evaluated. Kidney transplant recipients with evidence of calcineurin inhibitor toxicity were switched to a belatacept-based regimen dosed at 5mg/kg q2 two weeks for 2 months, and then monthly for 10 months; calcineurin inhibitor (CNI) was tapered off over 4 weeks. Mycophenolate mofetil and prednisone were continued per protocol. Patients were matched based on age, induction, and donor type with 10 control patients. Immune phenotype was analyzed by multiparameter flow cytometry. Alloreactive T cell memory was assessed by stimulating recipient T cells with irradiated donor B cells or donor cell lysate followed by intracellular cytokine secretion analysis to assess direct and indirect alloreactivity, respectively. EBV-and CMV-specific immunity was assessed by stimulation with peptide pools from the major viral antigens followed by intracellular cytokine secretion analysis. Statistical analysis was performed with JMP Pro11 using nonparametric testing.

Results: Immune phenotype (maturation subtype, T regulatory cells, activation, immune senescence, exhaustion) for CD4+ and CD8+ T cells did not differ at enrollment compared with 3, 6, and 12 months after belatacept start. Comparing patients switched to belatacept with the controls revealed a decreased frequency of terminally differentiated T cells after belatacept switch, median of 35.0% in belatacept and 43.9% in controls (p=0.006). Patients switched to belatacept had lower frequencies of senescent cells (CD8+CD57+KLRG1+), median of 24.0% compared with 41.5% in controls (p=0.002). Alloreactivity by direct and indirect assessment was low to undetectable and did not increase after switch. Antiviral immunity against CMV and EBV did not decrease after switch. There were no significant episodes of infection; two patients were treated for acute rejection (one belatacept, one control).

Conclusions: This study demonstrated that switch to belatacept was not associated with a change in immune phenotype, increase in the alloreactive immune response, or decrement in the antiviral immune response This may explain the mechanism behind costimulation blockade effectiveness without adverse infectious complications.

CITATION INFORMATION: Schaenman J, Rosetti M, Sidwell T, Groysberg V, Sunga G, Liang E, Gadzhyan J, Abdalla B, Lum E, Pham T, Dannovitch G, Veale J, Gritsch H, Reed E, Bunnapradist S. Stability of Immune Phenotype, Alloreactive, and Antiviral Immunity After Switch to Belatacept-Based Regimen After Kidney Transplantation. Am J Transplant. 2017;17 (suppl 3).

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