{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:15:11Z","timestamp":1789578911616,"version":"build-2803163510"},"reference-count":43,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD8+ T-cell activation has been demonstrated to distinguish patients with primary and infection-associated hemophagocytic lymphohistiocytosis (HLH) from patients with early sepsis. We evaluated the activation profile of CD8+ T cells in patients with various forms of secondary HLH (sHLH), including macrophage activation syndrome (MAS). Peripheral blood mononuclear cells from children with inactive systemic juvenile idiopathic arthritis (sJIA, n = 17), active sJIA (n = 27), MAS in sJIA (n = 14), infection-associated HLH (n = 7), and with other forms of sHLH (n = 9) were analyzed by flow cytometry. Compared with patients with active sJIA, in patients with MAS and sHLH of different origins, beside a significant increase in the frequency of CD38high\/HLA-DR+CD8+ T cells, we found a significant increase in the frequency of CD8+ T cells expressing the CD4 antigen (CD4dimCD8+ T cells). These cells expressed high levels of the activation markers CD38 and HLA-DR, suggesting they were a subset of CD38high\/HLA-DR+CD8+ T cells, as well as of the activation\/exhaustion markers CD25, PD1, CD95, and interferon-\u03b3. The frequency of CD4dimCD8+ T cells strongly correlated with most of the laboratory parameters of MAS severity and with circulating levels of CXCL9 and interleukin-18. These findings were confirmed in a prospective replication cohort in which no expansion of any particular T-cell receptor V\u03b2 family in CD3+ T cells of patients with sHLH was found. Finally, frequency of CD4dimCD8+, but not of CD38high\/HLA-DR+CD8+ T cells, significantly correlated with a clinical severity score, further supporting the involvement of these cells in MAS\/sHLH pathogenesis.<\/jats:p>","DOI":"10.1182\/blood.2021013549","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T19:03:12Z","timestamp":1651518192000},"page":"262-273","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":74,"title":["Expansion of CD4dimCD8+ T cells characterizes macrophage activation syndrome and other secondary HLH"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-4407","authenticated-orcid":false,"given":"Arianna","family":"De Matteis","sequence":"first","affiliation":[{"name":"1Division of 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