Session Time: 4:30pm-5:30pm
Presentation Time: 4:40pm-4:45pm
*Purpose: Preliminary data suggest solid organ transplant (SOT) recipients may be at high-risk for developing severe COVID-19. This may be due in part to alterations in T-cell physiology owing to use of immunosuppressive agents to prevent rejection. In this study we evaluated convalescent T-cell responses against SARS-CoV-2 in SOT recipients who had COVID-19.
*Methods: Peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood of 20 SOT recipients and 15 non-transplant controls (NTCs), all of whom had COVID >=14 days prior (convalescent samples). A total of 106 PBMCs were stimulated for 16 hours with megapools of overlapping 15mer peptides corresponding to the spike (S), nucleoprotein (NP) or membrane (Mb) protein of SARS-CoV-2 (each peptide at 5 μg/mL). After incubation, flow cytometry was performed for intracellular cytokines (IFN-γ, TNF-α, IL-2) and cell-surface T-cell exhaustion markers (CTLA4, PD-1, TIM-3). Total and SARS-CoV-2 antigen-specific CD4+ and CD8+ T-cells were identified. Polyfunctional T-cells were defined as those expressing ≥ 2 of the cytokines investigated.
*Results: The median age among SOT recipients was 54 years (range 24-86). The majority (15/20) were male, and kidney (12/20) transplant recipients. The majority (60.0%) of SOT recipients were hospitalized with COVID-19; three (15.0%) required ICU admission and mechanical ventilation. SOT recipients had significantly lower total CD4+ T-cells (51.6% vs. 62.2%, p=0.002) but significantly higher proportions of total CD8+ T-cells relative to NTCs (41.9% vs. 31.2% of live CD3+ cells, p=0.0016). SOT recipients also had significantly higher proportions of PD-1 on total CD4 (15.2% vs. 3.7%, p<0.0001) and CD8 T-cells (9.4% vs. 4.1% of live CD3+ cells, p=0.014). The majority of SOT recipients and NTCs generated S, NP and Mb specific CD4 and CD8 T-cells. More specifically, compared to NTCs, SOT recipients had increased proportions of IFN-γ, or IL-2 producing CD4+ T-cells, as well as polyfunctional CD4+ T-cells reactive to S peptides. SOT recipients also had increased proportions of IFN-γ, IL-2 or TNF-α producing CD4+ T-cells, and CD4+ polyfunctional T-cells reactive to NP peptides. NTCs were also characterized by lower proportions of IL-2 producing CD8+ T-cells reactive to S peptides. Hospitalization of SOT recipients (severe illness) was associated with higher proportions of total PD-1+ CD4 T-cells (22.2% vs 13.3% of CD4 T-cells, p=0.02) and low frequencies of CD8+ polyfunctional T-cells reactive to NP peptides (5.80 vs. 49.9 per 106 polyfunctional CD8 T-cells, p=0.014).
*Conclusions: Despite immune suppression, SOT recipients mount SARS-CoV-2 reactive T-cells at magnitudes often exceeding non-transplant controls. However, perturbations in global T-cell proportions, and increased expression of T-cell exhaustion markers, such as PD-1, may compromise the SARS-CoV-2-specific immune response.
To cite this abstract in AMA style:Ferreira VH, Marinelli TM, Ku T, Ierullo M, Majchrzak-Kita B, Bahinskaya I, Pinzon N, Humar A, Kumar D. T-Cell Responses in Solid Organ Transplant Recipients with SARS-CoV-2 Infection [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/t-cell-responses-in-solid-organ-transplant-recipients-with-sars-cov-2-infection/. Accessed August 3, 2021.
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