It has been proven that CD8+ T-cell activation can distinguish patients with primary and infection-associated hemophagocytic lymphohistiocytosis (HLH) from those with early sepsis. For a study, researchers analyzed the activation profile of CD8+ T cells in patients with secondary HLH (sHLH), like macrophage activation syndrome (MAS).

Flow cytometry was used to examine peripheral blood mononuclear cells from children with inactive sJIA (n=17), active sJIA (n=27), MAS in sJIA (n=14), infection-associated HLH (n=7), and different kinds of sHLH (n=9). As compared to patients having an active sJIA, in patients with MAS and sHLH of diverse origins, they identified a large rise in the frequency of CD8+ T cells expressing the CD4 antigen (CD4dimCD8+ T cells), in addition to a considerable increase in the frequency of CD38high/HLA-DR+CD8+ T cells. These cells had high levels of the activation indicators CD38 and HLA-DR, indicating that they belonged to a subset of CD38high/HLA-DR+CD8+ T cells, and the activation/exhaustion markers CD25, PD1, CD95, and interferon-γ.

Most laboratory indicators of MAS severity, and circulating levels of CXCL9 and interleukin-18, were linked with the frequency of CD4dimCD8+ T cells. The findings were validated in a prospective replication cohort, which exhibited no growth of any specific T-cell receptor Vβ family in CD3+ T cells from sHLH patients. Finally, the frequency of CD4dimCD8+ T cells was considerably linked with a clinical severity score but not with CD38high/HLA-DR+CD8+ T cells, confirming the role of these cells in MAS/sHLH pathogenesis.