Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T-cell activation, differentiation and repertoire
Standard
Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T-cell activation, differentiation and repertoire. / Ammann, Sandra; Lehmberg, Kai; Zur Stadt, Udo; Janka-Schaub, Gritta; Rensing-Ehl, Anne; Klemann, Christian; Heeg, Maximilian; Bode, Sebastian; Fuchs, Ilka; Ehl, Stephan; HLH study of the GPOH.
In: EUR J IMMUNOL, Vol. 47, No. 2, 02.2017, p. 364-373.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T-cell activation, differentiation and repertoire
AU - Ammann, Sandra
AU - Lehmberg, Kai
AU - Zur Stadt, Udo
AU - Janka-Schaub, Gritta
AU - Rensing-Ehl, Anne
AU - Klemann, Christian
AU - Heeg, Maximilian
AU - Bode, Sebastian
AU - Fuchs, Ilka
AU - Ehl, Stephan
AU - HLH study of the GPOH
N1 - © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2017/2
Y1 - 2017/2
N2 - 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.
AB - 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.
U2 - 10.1002/eji.201646686
DO - 10.1002/eji.201646686
M3 - SCORING: Journal article
C2 - 27925643
VL - 47
SP - 364
EP - 373
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 2
ER -
