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-γ. 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 Vβ 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.

De Matteis, A., Colucci, M., Rossi, M. N., Caiello, I., Merli, P., Tumino, N., Bertaina, V., Pardeo, M., Bracaglia, C., Locatelli, F., De Benedetti, F., Prencipe, G., Expansion of CD4dimCD8+ T cells characterizes macrophage activation syndrome and other secondary HLH, <<BLOOD>>, 2022; 140 (3): 262-273. [doi:10.1182/blood.2021013549] [https://hdl.handle.net/10807/228214]

Expansion of CD4dimCD8+ T cells characterizes macrophage activation syndrome and other secondary HLH

Locatelli, Franco
Writing – Review & Editing
;
2022

Abstract

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-γ. 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 Vβ 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.
2022
Inglese
De Matteis, A., Colucci, M., Rossi, M. N., Caiello, I., Merli, P., Tumino, N., Bertaina, V., Pardeo, M., Bracaglia, C., Locatelli, F., De Benedetti, F., Prencipe, G., Expansion of CD4dimCD8+ T cells characterizes macrophage activation syndrome and other secondary HLH, <<BLOOD>>, 2022; 140 (3): 262-273. [doi:10.1182/blood.2021013549] [https://hdl.handle.net/10807/228214]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/228214
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