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Age- and Sex-Mediated Differences in T Lymphocyte Populations of Kidney Transplant Recipients

R. Dziarmaga1, D. Ke1, V. Phan2, H. Cardinal3, R. Sapir-Pichhadze1, C. A. Piccirillo1, B. Mazer1, B. Foster1

1Research Institute - McGill University Health Centre, Montreal, QC, Canada, 2Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada, 3Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada

Meeting: 2020 American Transplant Congress

Abstract number: A-294

Keywords: Age factors, Kidney, T cells, T helper cells

Session Information

Date: Saturday, May 30, 2020

Session Name: Poster Session A: Biomarkers, Immune Assessment and Clinical Outcomes

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

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*Purpose: Kidney allograft failure rates peak between 17 to 24 years of age and are higher in young female than male kidney transplant recipients (KTR). We aimed to identify age- and sex-related differences in the immune systems of kidney transplant recipients (KTR) which may explain the age- and sex-related differences in kidney graft failure rates.

*Methods: Peripheral blood mononuclear cells (PBMC) were isolated from healthy controls (HC) and from KTR who were ≥1y post transplant, had stable graft function, no active acute infection, and were treated with maintenance immunosuppression. Effector T cells and regulatory T cells (Tregs) were analyzed by flow cytometry. We compared immune profiles between males and females across 3 groups: 3-10y (child), 11-16y (adolescent), and 17-29 y (adult).

*Results: Samples were obtained from 20 male KTR (6 child, 4 adolescent, 10 adult), 21 female KTR (3, 5, 13), 20 male HC (5, 5, 10), and 20 female HC (5, 5, 10). Th1 (IFNγ+ IL-4- IL-17a-) frequencies increased with age in male HC (children: 7.6%, adults: 13.1%, p=0.02), female HC (children: 7.2%, adults: 15.2%, p=0.004), and male KTR (children: 7.0%, adults: 14.8%, p=0.002). TNFα+ frequencies in CD4+ effector T cells increased with age in male HC (children: 11.4%, adults: 23.8%, p=0.01), female HC (children: 11.3%, adults: 23.0%, p=0.005), and male KTR (children: 17.4%, adults: 30.3%, p=0.03). Among adults, CD4+ FoxP3+ T cells in males showed higher Helios+ frequencies than in females for both HC (71.7% vs 62.3%, p=0.03) and KTR (65.2% vs 47.3%, p=0.006) (Fig. 1). Female adult HC showed higher Helios+ frequencies in their FoxP3+ T cells than KTR (62.3% vs 47.3%, p=0.02). Also among adults, FoxP3+ T cells in males showed higher TIGIT+ frequencies than females for KTR (54.5% vs 43.7%, p=0.03) but not HC (54.3% vs 48.5%, p=0.09).

*Conclusions: Increasing frequencies of inflammatory cytokine-producing effector CD4 T cells with increasing age correlates with increasing graft failure rates through childhood and adolescence. Among young adults, FoxP3+ T cells showed higher Helios+ and TIGIT+ frequencies in males than in females. This suggests that, among young adults, males have FoxP3+ T cells with greater suppressive capacity than FoxP3+ T cells in females. This may help explain why females have higher graft failure rates than males in this age group.

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To cite this abstract in AMA style:

Dziarmaga R, Ke D, Phan V, Cardinal H, Sapir-Pichhadze R, Piccirillo CA, Mazer B, Foster B. Age- and Sex-Mediated Differences in T Lymphocyte Populations of Kidney Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/age-and-sex-mediated-differences-in-t-lymphocyte-populations-of-kidney-transplant-recipients/. Accessed March 8, 2021.

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