Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T‐cell activation, differentiation and repertoire

Autor: Sandra Ammann, Maximilian Heeg, Sebastian F. N. Bode, Anne Rensing-Ehl, Stephan Ehl, Christian Klemann, Ilka Fuchs, Gritta Janka, Kai Lehmberg, Udo zur Stadt
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
T-Lymphocytes
Hemophagocytic lymphohistiocytosis
CD8-Positive T-Lymphocytes
Primary HLH
Lymphocyte Activation
Pathogenesis
CD57 Antigens
hemic and lymphatic diseases
Immunology and Allergy
Cytotoxic T cell
Cells
Cultured
biology
Research Article|Clinical
Hematopoietic Stem Cell Transplantation
Cell Differentiation
musculoskeletal system
medicine.anatomical_structure
Immunodeficiencies and autoimmunity
Virus Diseases
Female
Secondary HLH
hormones
hormone substitutes
and hormone antagonists
Research Article
Secondary Hemophagocytic Lymphohistiocytosis
endocrine system
T cell
Immunology
Receptors
Antigen
T-Cell
Lymphohistiocytosis
Hemophagocytic
03 medical and health sciences
Clinical
medicine
Humans
Interleukin-7 receptor
Perforin
fungi
Infant
Newborn
Infant
HLA-DR Antigens
medicine.disease
030104 developmental biology
HLA‐DR
T‐cell activation
Mutation
biology.protein
CD8
Zdroj: European Journal of Immunology
ISSN: 1521-4141
0014-2980
Popis: Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T‐cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V‐HLH). Polyclonal CD8+ T cells are highly activated in 1°HLH and 2°V‐HLH, but less in 2°HLH as assessed by HLA‐DR expression and marker combination with CD45RA, CCR7, CD127, PD‐1 and CD57. Absence of increased HLA‐DR expression on T cells excluded active 1° HLH with high sensitivity and specificity. A high proportion of polyclonal CD127−CD4+ T cells expressing HLA‐DR, CD57, and perforin is a signature of infants with 1°HLH, much less prominent in virus‐associated 2°HLH. The similar pattern and extent of CD8+ T‐cell activation compared to 2° V‐HLH is compatible with a viral trigger of 1°HLH. However, in most 1°HLH patients no triggering infection was documented and the unique activation of cytotoxic CD4+ T cells indicates that the overall T‐cell response in 1°HLH is different. This may reflect different pathways of pathogenesis of these two HLH variants.
The illustrated phenotype is characteristic for patients presenting with different subtypes of HLH in the first year of life and demonstrates the pathophysiological principle. In older patients, most markers of T cell differentiation (apart from HLA‐DR) are very heterogenous also in healthy individuals, such that these phenotypic markers are of limited diagnostic value in patients beyond infancy.
Databáze: OpenAIRE
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