Cytokine flexibility of early and differentiated memory T helper cells in juvenile idiopathic arthritis.
OBJECTIVE
It has been suggested that CD45RO+CD27+ T cells represent recently activated memory cells, whereas CD45RO+CD27- T cells are activated memory T cells in the process of differentiating into effector cells. We investigated (1) CCR7 and CCR5 expression and (2) modulation of cytokine expression in "early" (CD27+) and "differentiated" (CD27-) memory CD4+ T cells from peripheral blood and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).


METHODS
SF CD4+CD45RO+CD27+ and CD27- memory T cells from 6 patients with JIA were tested by flow cytometry for intracellular interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) after in vitro priming with CD3 and CD28 mAb in the presence of IL-4, and subsequent culture with IL-2.


RESULTS
SF CD4+CD45RO+CD27+ cells contained higher proportions of CCR7+ (median 46% vs 23%) and lower proportions of CCR5+ (73% vs 90%) cells than paired CD27- T cells. Both CD27+ and CD27- memory T helper cells from SF displayed a higher IFN-gamma/IL-4 ratio than their peripheral blood counterparts. No significant difference was observed in the percentage of IFN-gamma-expressing cells between CD27+ (32%, range 4-47%) and CD27- (29.4%, range 5-52%) memory T helper cells from SF.


CONCLUSIONS
Irrespective of their differentiation stage, both CD27+ and CD27- SF memory T helper cells were found to switch from a proinflammatory to an antiinflammatory pattern of cytokine production.
2nd Division of Pediatrics, "G. Gaslini" Scientific Institute for Children, Genoa, Italy.
Sabrina
S
Chiesa
Ignazia
I
Prigione
Fabio
F
Morandi
Antonella
A
Buoncompagni
Paolo
P
Picco
Paola
P
Bocca
Alberto
A
Martini
Vito
V
Pistoia
Marco
M
Gattorno
D001171:Arthritis, Juvenile / Q000276:immunology*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D019713:Receptors, CCR5 / Q000276:immunology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
C515370:CCR7 protein, human; D016207:Cytokines; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens