Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7.
BACKGROUND
Adhesion molecules and chemokine receptors are involved in tissue-specific homing of T cells to the skin and play an important role in the pathophysiology of cutaneous lymphoma. It has recently been reported that the chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the chemokine receptor CCR10.


OBJECTIVE
To investigate the expression of CCR4, CCR7 and CCR10 on skin-homing CLA(+) and CD4(+) T cells in the peripheral blood of patients with Sezary syndrome (SS), a rare leukaemic variant of cutaneous T-cell lymphoma.


METHODS
Lymphocytes from five patients with SS, six patients with mycosis fungoides and four healthy volunteers were isolated and analysed using flow cytometry. Additionally, the T-cell receptor (TCR)-Vbeta CDR3 regions were cloned and sequenced in two patients.


RESULTS
We found that CCR4 is expressed on almost all CLA(+) and CD4(+) memory T cells. Using monoclonal antibodies specific for single TCR-Vbeta chains we identified malignant T cells in four patients with SS. Importantly, we found that most but not all malignant Sezary cells expressed the skin-homing chemokine receptor CCR10. Additionally, we found that a significant proportion of these cells also expressed the lymph node-homing chemokine receptor CCR7.


CONCLUSIONS
Our results support the concept that chemokine receptors play an important role in the pathophysiology of SS and suggest that the malignant clone may represent an expansion of skin-homing cutaneous 'central' memory T cells in the peripheral blood of these patients.
Sokolowska-Wojdylo
M
M
Laboratory of Experimental Dermatology, Department of Dermatology, Rheinische Friedrich Wilhelm-University, Sigmund Freud Str. 25, 53105 Bonn, Germany.
Wenzel
J
J
Gaffal
E
E
Lenz
J
J
Speuser
P
P
Erdmann
S
S
Abuzahra
F
F
Bowman
E
E
Roszkiewicz
J
J
Bieber
T
T
Tüting
T
T
D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000097:blood*; D012751:Sezary Syndrome / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C515706:CCR10 protein, human; C515354:CCR4 protein, human; C515370:CCR7 protein, human; C063419:CTAGE1 protein, human; D022801:Complementarity Determining Regions; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D019707:Receptors, Chemokine