Lymphocyte-independent pathways underlie the pathogenesis of murine cytomegalovirus-associated secondary hemophagocytic lymphohistiocytosis (original) (raw)

Hemophagocytic lymphohistiocytosis (HLH) constitutes a spectrum of immunological disorders characterized by uncontrolled immune activation and key symptoms such as fever, splenomegaly, pancytopenia, hemophagocytosis, hyperferritinemia and hepatitis. In genetic or primary HLH, hyperactivated CD8+ T cells are the main drivers of pathology. However, in acquired, secondary HLH, the role of lymphocytes remains vague. In the present study the involvement of lymphocytes in the pathogenesis of a cytomegalovirus-induced model of secondary HLH was explored. We previously reported CD8+ T cells to be redundant in this model and therefore focused on CD4+ helper and regulatory T cells. CD4+ T cells were markedly activated and skewed towards a pro-inflammatory Thelper 1 transcription profile in mice displaying a severe and complete HLH phenotype. Counter to expectations, regulatory T cells were not reduced in numbers and were in fact more activated. Therapeutic strategies targeting CD25high hypera...