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. 2021 Mar 15;22(6):2975.
doi: 10.3390/ijms22062975.

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Erasmia Sampani  1 , Dimitra-Vasilia Daikidou  1 , George Lioulios  1 , Aliki Xochelli  2 , Zoi Mitsoglou  1 , Vasiliki Nikolaidou  2 , Chrysostomos Dimitriadis  1 , Asimina Fylaktou  2 , Aikaterini Papagianni  1 , Maria Stangou  1
Affiliations

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Erasmia Sampani et al. Int J Mol Sci. .

Abstract

Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients.

Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD).

Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%-24%) vs. 4.1% (0-42.3%), p = 0.02 and 61.3% (24%-76%) vs. 43% (5.7%-85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14-100) to 52.7 (15-203), p = 0.02; and CD8 + CD28null cells, from 137 (56-275) to 266 (103-456), p = 0.01.

Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD.

Keywords: CD28null cells; diabetes mellitus; end-stage renal disease; lymphocytes; regulatory T cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Total numbers of (A) white cells, (B) neutrophils (%), and (C) lymphocytes (%) in DM, NDM, and controls. + p NDM vs. controls <0.01, ++ p DM vs. controls <0.0001.
Figure 2
Figure 2
(A, B) CD3+CD4+ percentage and total count, and (C, D) CD3+CD8+ percentage and total count in DM, NDM, and controls.
Figure 3
Figure 3
Differences in percentage of (A) CD4+CD28null cells, (B) CD8+CD28null cells, and (C) total CD28null cells between DM, NDM, and controls. * p DM vs. controls <0.0001, ** p DM vs. NDM <0.04, ^ p NDM vs. controls 0.04, ^^ p DM vs. controls <0.0001.
Figure 4
Figure 4
Differences in percentage and total cell count in (A,B) NK cells and (C,D) Tregs in DM, NDM, and controls, * p (DM vs. controls) = 0.03, ** p (DM vs. controls) = 0.001, ^ p (DM vs. controls) = 0.02, ^^ p (DM vs. controls) = 0.001.
Figure 5
Figure 5
Description of gating process. (A) Gating of lymphocytes and identification of (B) CD3+, (C) CD3+CD4+, (D) CD3+CD8+, (E) CD3–CD(16+56)+ cells, CD28– cells on CD4+ population, (F) CD4+CD28null cells and CD28– cells in CD8+ population, (G) CD8+CD28null cells.
Figure 6
Figure 6
FOXP-3 assay—description of gating process. (A) Gating of lymphocytes. Identification of (B) CD4+, (C) FOXP-3 (+), and (D) CD4+CD25+ cells; (E) identification of normal Tregs on CD4+ cells.
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