Serum Immunoinhibitory Factors in Stroke Patients

Kostić, Vladimir; Mostarica-Stojković, Marija; Ramić, Zorica; Kovăcević, Miroslav; Lukić, Miodrag L.

doi:10.1159/000116296

Cited by 6 publications

(3 citation statements)

References 8 publications

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“…Consistent with prior reports 31 , visual observations suggested decreased proliferative activity in lymphocyte cultures treated with unmanipulated ischemic stroke serum relative to those treated with unmanipulated serum from control groups, as they appeared to contain smaller and more diffuse clusters of blasting lymphocytes. However, visual indications suggested that the inhibitory effect of ischemic stroke serum was at least moderately counteracted by depletion of sCD163 (Fig.…”

Section: Resultssupporting

confidence: 89%

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

O’Connell

Tennant

Lucke-Wold

et al. 2017

Sci Rep

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CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.

show abstract

Section: Resultssupporting

confidence: 89%

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

O’Connell

Tennant

Lucke-Wold

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Consistent with prior reports, 31 visual observations suggested decreased proliferative activity in lymphocyte cultures treated with unmanipulated ischemic stroke serum relative to those treated with unmanipulated serum from control groups, as they appeared to contain smaller and more diffuse clusters of blasting lymphocytes. However, visual indications suggested that the inhibitory effect of ischemic stroke serum was at least moderately counteracted by depletion of sCD163 ( Figure 5B).…”

Section: Stroke-induced Elevations In Circulating Scd163 Suppress Lymsupporting

confidence: 90%

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

O’Connell

Tennant

Lucke-Wold

et al. 2017

Preprint

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CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n=39), neurologically asymptomatic controls (n=20), and stroke mimics (n=20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this strokeinduced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes.Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon. PREPRINT

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“…Thereafter, strong evidence from clinical studies has shown that stroke causes a reduction of T cells in the peripheral blood and inhibition of T cell proliferation in response to antigen stimulation, as well as inhibition of the delayed type hypersensitivity (DTH) skin test [7]. Most studies agree that T-cell-mediated immunity is significantly inhibited by brain injury from stroke [7], [8], [9], [10], [11]. However, there are contradictory reports about the effects of stroke on humoral immunity in human patients.…”

Section: Introductionmentioning

confidence: 99%

T Cells Contribute to Stroke-Induced Lymphopenia in Rats

Xiong

Wei

et al. 2013

PLoS ONE

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Stroke-induced immunodepression (SIID) results when T cell and non-T immune cells, such as B cells, NK cells and monocytes, are reduced in the peripheral blood and spleen after stroke. We investigated the hypothesis that T cells are required for the reductions in non-T cell subsets observed in SIID, and further examined a potential correlation between lymphopenia and High-mobility group protein B1 (HMGB1) release, a protein that regulates inflammation and immunodepression. Our results showed that focal ischemia resulted in similar cortical infarct sizes in both wild type (WT) Sprague Dawley (SD) rats and nude rats with a SD genetic background, which excludes the possibility of different infarct sizes affecting SIID. In addition, the numbers of CD68-positive macrophages in the ischemic brain did not differ between WT and nude rats. Numbers of total peripheral blood mononuclear cells (PBMCs) or splenocytes and lymphocyte subsets, including T cells, CD4+ or CD8+ T cells, B cells and monocytes in the blood and spleen, were decreased after stroke in WT rats. In nude rats, however, the total number of PBMCs and absolute numbers of NK cells, B cells and monocytes were increased in the peripheral blood after stroke; nude rats are athymic therefore they have few T cells present. Adoptive transfer of WT splenocytes into nude rats before stroke resulted in lymphopenia after stroke similar to WT rats. Moreover, in vitro T cell proliferation stimulated by Concanavalin A was significantly inhibited in WT rats as well as in nude rats receiving WT splenocyte adoptive transfer, suggesting that T cell function is indeed inhibited after stroke. Lastly, we demonstrated that stroke-induced lymphopenia is associated with a reduction in HMGB1 release in the peripheral blood. In conclusion, T cells are required for stroke-induced reductions in non-T immune cells and they are the most crucial lymphocytes for SIID.

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Serum Immunoinhibitory Factors in Stroke Patients

Cited by 6 publications

References 8 publications

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

T Cells Contribute to Stroke-Induced Lymphopenia in Rats

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