Circulating CXCR5<sup>+</sup>CD4<sup>+</sup>helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production

Zhang, X; Lindwall, Elvira; Gauthier, Carl; Lyman, Justin; Spencer, Nakia D.; Alarakhia, Anika; Fraser, Austin; Ing, Sharon; Chen, M; Webb-Detiege, Tamika; Zakem, Jerald; Davis, William E.; Choi, Yong Sung; Quinet, Robert

doi:10.1177/0961203314567750

Cited by 116 publications

(96 citation statements)

References 42 publications

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“…This pattern was associated with greater CD4 Tfh cell numbers, sustained autoantibody production and severe lupus nephritis. These results are consistent with reports that Tfh cells are increased in lupus (48) and that strong T cell stimulation is needed for Th1 differentiation but is not needed for Tfh cell differentiation (49). Differential immune skewing of donor T cells was not secondary to host NK cell function.…”

Section: Discussionsupporting

confidence: 93%

Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

Soloviova

Puliaiev

Haas

et al. 2015

The Journal of Immunology

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Using the parent-into-F1 model of induced lupus and (C57Bl/6xDBA2) F1 mice as hosts, we compared the inherent lupus-inducing properties of the two parental strain CD4 T cells. To control for donor CD4 recognition of alloantigen, we used H-2d identical DBA/2 and B10.D2 donor T cells. We demonstrate that these two normal, non-lupus prone parental strains exhibit two different T cell activation pathways in vivo. B10.D2 CD4 T cells induce a strong Th1/CMI pathway characterized by IL-2/IFN-g expression, help for CD8 CTL, skewing of DC subsets towards CD8a DC, coupled with reduced CD4Tfh cells and transient B cell help. By contrast, DBA/2 CD4 T cells exhibit a reciprocal, lupus-inducing pathway characterized by poor IL-2/IFN-g expression, poor help for CD8 CTL, skewing of DC subsets towards pDC coupled with greater CD4 Tfh cells, prolonged B cell activation, autoantibody formation, and lupus-like renal disease. Additionally, two distinct in vivo splenic gene expression signatures were induced. In vitro analysis of TCR signaling revealed defective DBA CD4 T cell induction of NF-κB, reduced degradation of IκBα and increased expression of the NF-κB regulator A20. Thus, attenuated NF-κB signaling may lead to diminished IL-2 production by DBA CD4 T cells. These results indicate that intrinsic differences in donor CD4 IL-2 production and subsequent immune skewing could contribute to lupus susceptibility in humans. Therapeutic efforts to skew immune function away from excessive help for B cells and towards help for CTL may be beneficial.

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Section: Discussionsupporting

confidence: 93%

Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

Soloviova

Puliaiev

Haas

et al. 2015

The Journal of Immunology

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“…Leptin is closely related to adipokines, which are associated with oxidative stress and are reported to be overproduced in SLE patients [39, 40]. Previous data indicate that leptin signaling modulates T cell proliferation and preferential differentiation of Th1 cells over Th2 cells [41–43].…”

Section: Oxidative Stress and Treg Cellsmentioning

confidence: 99%

Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus

Yang

Zou

et al. 2016

Oxidative Medicine and Cellular Longevity

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Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. The pathogenic mechanisms that cause SLE remain unclear; however, it is well recognized that the immune balance is disturbed and that this imbalance contributes to the autoimmune symptoms of SLE. Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and the ability of the biological system to readily detoxify the reactive intermediates or to repair the resulting damage. In humans, oxidative stress is involved in many diseases, including atherosclerosis, myocardial infarction, and autoimmune diseases. Numerous studies have confirmed that oxidative stress plays an important role in the pathogenesis of SLE. This review mainly focuses on the recent research advances with respect to oxidative stress and regulatory T (Treg)/helper T 17 (Th17) cell dysfunction in the pathogenesis of SLE.

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“…A previous study found that patients who had received a propofol infusion had a higher percentage of T helper cells,12 but the physiological significance of this has not been elucidated. Recently, researchers found a new type of cells called circulating T helper-like follicular cells in the blood of SLE patients 13. These cells shared similar phenotypic properties with germinal centre follicular helper T cells which could drive B cells to differentiate into IgG secreting plasma cells.…”

Section: Discussionmentioning

confidence: 99%

Progression of systemic lupus erythematosus associated with propofol administration: a case report

Gui

Xiong

et al. 2017

Eur J Hosp Pharm

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Propofol is a sedative-hypnotic agent used as a general anaesthetic with a good safety profile. However, the potential risk for patients with systemic lupuserythematosus (SLE) receiving propofol remains unclear. We report the case of a patient who received an intravenous infusion of propofol for painless gastroscopy which exacerbated acute SLE despite no history of allergies. The adverse effect might be because propofol increased T helper cells and trigged the induction of B cell differentiation and plasmablast formation, which further promoted the secretion of auto-antibodies. This case shows that propofol can exacerbate SLE symptoms in some patients and highlights the importance of identifying potential immune-related factors before propofol administration, especially in patients with autoimmune diseases. It is important to be aware of and differentiate this uncommon and non-specific SLE manifestation from a myriad of disorders presenting with a primary digestive disorder in the outpatient clinic.

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Circulating CXCR5⁺CD4⁺helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production

Cited by 116 publications

References 42 publications

Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus

Progression of systemic lupus erythematosus associated with propofol administration: a case report

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Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production

Cited by 116 publications

References 42 publications

Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus

Progression of systemic lupus erythematosus associated with propofol administration: a case report

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Circulating CXCR5⁺CD4⁺helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production