Down-regulation of CD5 expression on activated CD8+ T cells in familial hemophagocytic lymphohistiocytosis with perforin gene mutations.
Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled activation of T cells and macrophages with overproduction of cytokines. Familial HLH type 2 (FHL2) is the most common form of primary HLH and is caused by mutations in PRF1. We have recently described a significant increase in the subpopulation of CD8(+) T cells with clonal expansion and CD5 down-regulation in Epstein-Barr virus associated-HLH, which represented a valuable tool for its diagnosis. However, this unusual phenotype of CD8(+) T cells has not been investigated fully in patients with FHL2. We performed immunophenotypic analysis of peripheral blood and measured serum pro-inflammatory cytokines in five patients with FHL2. All patients showed significantly increased subpopulations of activated CD8(+) T cells with down-regulation of CD5, which were negligible among normal controls. Analysis of T-cell receptor Vβ repertoire suggested the reactive and oligoclonal expansion of these cells. The proportion of the subset declined after successful treatment concomitant with reduction in the serum levels of cytokines in all patients except one who continued to have a high proportion of the subset and died. These findings suggest that down-regulation of CD5 on activated CD8(+) T cells may serve as a useful marker of dysregulated T cell activation and proliferation in FHL2.
Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. Electronic address: taizo@staff.kanazawa-u.ac.jp.
Taizo
T
Wada
Yasuhisa
Y
Sakakibara
Ryosei
R
Nishimura
Tomoko
T
Toma
Yasuhisa
Y
Ueno
Seiki
S
Horita
Taihei
T
Tanaka
Masanori
M
Nishi
Keisuke
K
Kato
Takahiro
T
Yasumi
Osamu
O
Ohara
Akihiro
A
Yachie
D018956:CD5 Antigens / Q000235:genetics* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002675:Child, Preschool; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D008297:Male; D009154:Mutation; D054353:Perforin / Q000235:genetics* / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D018956:CD5 Antigens; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin
EBV; Epstein-Barr virus; FHL; HLA; HLH; IM; NK; PBMCs; PE; T-cell receptor; TCR; familial hemophagocytic lymphohistiocytosis; hemophagocytic lymphohistiocytosis; human leukocyte antigen; infectious mononucleosis; mAb; monoclonal antibody; natural killer; peripheral blood mononuclear cells; phycoerythrin