CD4 T lymphocyte subsets display heterogeneous susceptibility to apoptosis induced by serum from patients with systemic lupus erythematosus.
Apoptosis
Helper T cells
Regulatory T cells
Systemic lupus erythematosus
T lymphocyte
Journal
Advances in rheumatology (London, England)
ISSN: 2523-3106
Titre abrégé: Adv Rheumatol
Pays: England
ID NLM: 101734172
Informations de publication
Date de publication:
16 08 2023
16 08 2023
Historique:
received:
13
12
2022
accepted:
09
08
2023
medline:
18
8
2023
pubmed:
17
8
2023
entrez:
16
8
2023
Statut:
epublish
Résumé
Serum from systemic lupus erythematosus (SLE) patients has been shown to induce T-lymphocyte (TL) apoptosis. Given that different cells of the immune system display different sensitivity to apoptosis, we set to evaluate the in vitro effect of SLE serum on regulatory T-cells (Treg), Th17, Th1 and Th2 from SLE patients and healthy controls. Peripheral blood mononuclear cells from SLE patients or normal controls were exposed to a pool of sera from SLE patients or normal controls. Annexin V was used to label cells in apoptosis or necrosis. Annexin V-labeled Treg, Th17, Th1 and Th2 cells were determined using flow cytometry. Total CD3 + and CD4 + cells from SLE patients showed higher frequency of spontaneous apoptosis/necrosis, whereas Th1 cells from SLE patients presented reduced spontaneous apoptosis/necrosis rate as compared with cells from controls. Incubation with SLE serum induced increased frequency of apoptotic/necrotic CD3 + , CD4 + and Th2 cells from normal controls or from SLE patients as compared with cultures incubated with normal human serum (NHS) or without human serum at all. Incubation with SLE serum did not increase the apoptosis/necrosis rate in Th1 or Th17 cells. Treg cells from SLE patients were more prone to apoptosis/necrosis induced by SLE serum than Treg cells from normal individuals. Th1, Th2, and Th17 cells presented increased apoptosis rates in cultures without human serum. Our findings indicate that the serum of patients with active SLE stimulates apoptosis of CD4 + T cells in general and exhibit differentiated effects on CD4 + T-cell subsets.
Sections du résumé
BACKGROUND
Serum from systemic lupus erythematosus (SLE) patients has been shown to induce T-lymphocyte (TL) apoptosis. Given that different cells of the immune system display different sensitivity to apoptosis, we set to evaluate the in vitro effect of SLE serum on regulatory T-cells (Treg), Th17, Th1 and Th2 from SLE patients and healthy controls.
METHODS
Peripheral blood mononuclear cells from SLE patients or normal controls were exposed to a pool of sera from SLE patients or normal controls. Annexin V was used to label cells in apoptosis or necrosis. Annexin V-labeled Treg, Th17, Th1 and Th2 cells were determined using flow cytometry.
RESULTS
Total CD3 + and CD4 + cells from SLE patients showed higher frequency of spontaneous apoptosis/necrosis, whereas Th1 cells from SLE patients presented reduced spontaneous apoptosis/necrosis rate as compared with cells from controls. Incubation with SLE serum induced increased frequency of apoptotic/necrotic CD3 + , CD4 + and Th2 cells from normal controls or from SLE patients as compared with cultures incubated with normal human serum (NHS) or without human serum at all. Incubation with SLE serum did not increase the apoptosis/necrosis rate in Th1 or Th17 cells. Treg cells from SLE patients were more prone to apoptosis/necrosis induced by SLE serum than Treg cells from normal individuals. Th1, Th2, and Th17 cells presented increased apoptosis rates in cultures without human serum.
CONCLUSION
Our findings indicate that the serum of patients with active SLE stimulates apoptosis of CD4 + T cells in general and exhibit differentiated effects on CD4 + T-cell subsets.
Identifiants
pubmed: 37587510
doi: 10.1186/s42358-023-00321-3
pii: 10.1186/s42358-023-00321-3
doi:
Substances chimiques
Annexin A5
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
40Informations de copyright
© 2023. Sociedade Brasileira de Reumatologia.
Références
Perniok A, Wedekind F, Herrmann M, Specker C, Schneider M. High levels of circulating early apoptic peripheral blood mononuclear cells in systemic lupus erythematosus. Lupus. 1998;7(2):113–8.
doi: 10.1191/096120398678919804
pubmed: 9541096
Yang F, He Y, Zhai Z, Sun E. Programmed cell death pathways in the pathogenesis of systemic lupus erythematosus. J Immunol Res. 2019;2019:3638562.
doi: 10.1155/2019/3638562
pubmed: 31871956
pmcid: 6913273
Emlen W, Niebur J, Kadera R. Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol Baltim Md. 1994;152(7):3685–92.
Lorenz HM, Grünke M, Hieronymus T, Herrmann M, Kühnel A, Manger B, et al. In vitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases. Arthritis Rheum. 1997;40(2):306–17.
doi: 10.1002/art.1780400216
pubmed: 9041943
Bengtsson AA, Sturfelt G, Gullstrand B, Truedsson L. Induction of apoptosis in monocytes and lymphocytes by serum from patients with systemic lupus erythematosus—an additional mechanism to increased autoantigen load? Clin Exp Immunol. 2004;135(3):535–43.
doi: 10.1111/j.1365-2249.2003.02386.x
pubmed: 15008990
pmcid: 1808958
Bengtsson AA, Gullstrand B, Truedsson L, Sturfelt G. SLE serum induces classical caspase-dependent apoptosis independent of death receptors. Clin Immunol. 2008;126(1):57–66.
doi: 10.1016/j.clim.2007.10.003
pubmed: 18036993
Wang H, Xu J, Ji X, Yang X, Sun K, Liu X, et al. The abnormal apoptosis of T cell subsets and possible involvement of IL-10 in systemic lupus erythematosus. Cell Immunol. 2005;235(2):117–21.
doi: 10.1016/j.cellimm.2005.08.031
pubmed: 16226734
Yang BC, Wang YS, Lin LC, Liu MF. Induction of apoptosis and cytokine gene expression in T-cell lines by sera of patients with systemic lupus erythematosus. Scand J Immunol. 1997;45(1):96–102.
doi: 10.1046/j.1365-3083.1997.d01-371.x
pubmed: 9010506
Tiefenthaler M, Bacher N, Linert H, Mühlmann O, Hofer S, Sepp N, et al. Apoptosis of CD34+ cells after incubation with sera of leukopenic patients with systemic lupus erythematosus. Lupus. 2003;12(6):471–8.
doi: 10.1191/0961203303lu423oa
pubmed: 12873050
Klint C, Truedsson L, Andreasson A, Johansson I, Sturfelt G. Toxic effects of SLE serum on normal monocytes in vitro: cell death induced by apoptosis related to complement dysfunction. Lupus. 2000;9(4):278–87.
doi: 10.1191/096120300680198999
pubmed: 10866099
Georgescu L, Vakkalanka RK, Elkon KB, Crow MK. Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas ligand. J Clin Invest. 1997;100(10):2622–33.
doi: 10.1172/JCI119806
pubmed: 9366578
pmcid: 508464
Xue C, Lan-Lan W, Bei C, Jie C, Wei-Hua F. Abnormal Fas/FasL and caspase-3-mediated apoptotic signaling pathways of T lymphocyte subset in patients with systemic lupus erythematosus. Cell Immunol. 2006;239(2):121–8.
doi: 10.1016/j.cellimm.2006.05.003
pubmed: 16808908
Zhang X, Brunner T, Carter L, Dutton RW, Rogers P, Bradley L, et al. Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis. J Exp Med. 1997;185(10):1837–49.
doi: 10.1084/jem.185.10.1837
pubmed: 9151709
pmcid: 2196321
Yu Y, Iclozan C, Yamazaki T, Yang X, Anasetti C, Dong C, et al. Abundant c-Fas–associated death domain–like interleukin-1–converting enzyme inhibitory protein expression determines resistance of T helper 17 cells to activation-induced cell death. Blood. 2009;114(5):1026–8.
doi: 10.1182/blood-2009-03-210153
pubmed: 19429865
pmcid: 2721783
Funauchi M, Sugiyama M, SukYoo B, Ikoma S, Ohno M, Kinoshita K, et al. A possible role of apoptosis for regulating autoreactive responses in systemic lupus erythematosus. Lupus. 2001;10(4):284–8.
doi: 10.1191/096120301680416977
pubmed: 11341105
Pan X, Yuan X, Zheng Y, Wang W, Shan J, Lin F, et al. Increased CD45RA+ FoxP3(low) regulatory T cells with impaired suppressive function in patients with systemic lupus erythematosus. PLoS ONE. 2012;7(4): e34662.
doi: 10.1371/journal.pone.0034662
pubmed: 22506043
pmcid: 3323568
Yang J, Chu Y, Yang X, Gao D, Zhu L, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009;60(5):1472–83.
doi: 10.1002/art.24499
pubmed: 19404966
Shin MS, Lee N, Kang I. Effector T-cell subsets in systemic lupus erythematosus: update focusing on Th17 cells. Curr Opin Rheumatol. 2011;23(5):444–8.
doi: 10.1097/BOR.0b013e328349a255
pubmed: 21720245
pmcid: 3489922
Mesquita D, de Melo CW, Araujo J, Pucci F, Salmazi K, Kallas E, et al. Systemic lupus erythematosus exhibits a dynamic and continuum spectrum of effector/regulatory T cells. Scand J Rheumatol. 2011;40(1):41–50.
doi: 10.3109/03009742.2010.489229
pubmed: 20936986
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86.
doi: 10.1002/art.34473
pubmed: 22553077
pmcid: 3409311