Abstract Number: OC 04.3
Meeting: ISTH 2020 Congress
Background: Ischemic stroke is a leading cause of morbidity and mortality worldwide. Recanalization of the occluded vessel is essential, but not sufficient to guarantee brain salvage. Infarcts often develop further due to a thrombo-inflammatory process critically involving platelets and T cells, but the underlying mechanisms are unknown.
CD84 is a member of the SLAM family and acts as a homophilic cell adhesion molecule highly expressed on platelets and on different immune cell populations, where it acts a co-receptor.
Aims: We aimed to assess a potential contribution of CD84 to infarct growth following experimental stroke.
Methods: Mice lacking CD84 either constitutively or on their platelets were subjected to the transient middle cerebral artery occlusion (tMCAO) model and immune cell infiltration into the brain, as well as infarct sizes were determined. Wild-type (WT) and Cd84-/- CD4+ T cells were adoptively transferred into lymphocyte-deficient mice (Rag1-/-) prior to tMCAO. The motility of WT and Cd84-/- T cells in response to platelet releasate or recombinant CD84 was measured in vitro. CD84 expression on human platelets (determined locally in the ischemic brain and systemically) and stroke severity were assessed in a small clinical cohort.
Results: Cd84-/- mice, as well as mice lacking CD84 on either platelets or T cells displayed reduced cerebral CD4+ T cell infiltration and less occluded vessels following experimental stroke, resulting in reduced neurological damage. Platelet-derived soluble CD84 enhanced motility of WT, but not of Cd84-/- CD4+ T cells in vitro suggesting homophilic CD84 interactions to drive this process. In a clinical study, human arterial blood directly sampled from the ischemic cerebral circulation indicated local shedding of platelet CD84. Moreover, high platelet CD84 expression levels were associated with poor outcome in stroke patients.
Conclusions: These results establish CD84 as a critical pathogenic effector and thus a potential pharmacological target in ischemic stroke.
To cite this abstract in AMA style:Stegner D, Schuhmann MK, Stoll G, Bieber M, Vögtle T, Hofmann S, Seyhan M, Kollikowski AM, Klaus V, Heuschmann P, Pham M, Nieswandt B. CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-inflammation in Acute Stroke [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/cd84-links-t-cell-and-platelet-activity-in-cerebral-thrombo-inflammation-in-acute-stroke/. Accessed March 4, 2024.
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