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Lymphocyte-independent pathways underlie the pathogenesis of murine cytomegalovirus-associated secondary haemophagocytic lymphohistiocytosis.

Abstract：

:Haemophagocytic lymphohistiocytosis (HLH) constitutes a spectrum of immunological disorders characterized by uncontrolled immune activation and key symptoms such as fever, splenomegaly, pancytopenia, haemophagocytosis, hyperferritinaemia 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 have 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 activated markedly and skewed towards a proinflammatory T helper type 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 hyperactivated T cells were ineffective to alleviate disease, indicating that T cell hyperactivation is not a pathogenic factor in cytomegalovirus-induced murine HLH. Moreover, even though T cells were essential in controlling viral proliferation, CD4+ T cells, in addition to CD8+ T cells, were dispensable in the development of the HLH-like syndrome. In fact, no T or B cells were required for induction and propagation of HLH disease, as evidenced by the occurrence of cytomegalovirus-associated HLH in severe combined immunodeficient (SCID) mice. These data suggest that lymphocyte-independent mechanisms can underlie virus-associated secondary HLH, accentuating a clear distinction with primary HLH.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Brisse E,Imbrechts M,Mitera T,Vandenhaute J,Berghmans N,Boon L,Wouters C,Snoeck R,Andrei G,Matthys P

doi

10.1111/cei.13084

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

104-119

issue

eissn

0009-9104

issn

1365-2249

journal_volume

192

pub_type

杂志文章

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Lymphocyte-independent pathways underlie the pathogenesis of murine cytomegalovirus-associated secondary haemophagocytic lymphohistiocytosis.