CD8 T Cell Memory Increases Immunopathology in the Perforin-Deficient Model of Hemophagocytic Lymphohistiocytosis Secondary to TNF-α
2018
Familial
hemophagocytic lymphohistiocytosistype 2 (
FHL2) is a
cytokine stormsyndrome characterized by immune
hyperactivationwith viral infection due to a CD8 T cell cytotoxic killing defect secondary to a
perforindeficiency. As most studies of
FHL2mice have used pathogen-naive animals, the effects of immune memory on
FHL2are understudied. We used an immunization model of the
perforin-deficient mouse to study the effects of immune memory on
FHL2. Prior CD8 T cell–specific Ag exposure leads to enhanced
hemophagocytic lymphohistiocytosiswith increased morbidity and decreased time to mortality. Enhanced disease is associated with altered cytokine production and T cell proliferation. Response to IFN-γ blockade is reduced and TNF - α gains a pathogenic role, although blockade of the IL-33 receptor ST2 remains effective. These results suggest that pre-existing immune memory may worsen the outcome and alter the treatment response for
FHL2patients who may not be naive to their immune triggers.
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