Cytokine Flexibility of Early and Differentiated Memory T Helper Cells in Juvenile Idiopathic Arthritis

SABRINA CHIESA, IGNAZIA PRIGIONE, FABIO MORANDI, ANTONELLA BUONCOMPAGNI, PAOLO PICCO, PAOLA BOCCA, ALBERTO MARTINI, VITO PISTOIA, and MARCO GATTORNO

ABSTRACT.

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-g (IFN-g) 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-g/IL-4 ratio than their peripheral blood counterparts. No significant difference was observed in the percentage of IFN-g-expressing cells between CD27+ (32%, range 4–47%) and CD27– (29.4%, range 5–52%) memory T helper cells from SF.

Conclusion. 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. (J Rheumatol 2004;31:2048-54)

Key Indexing Terms:

MEMORY T LYMPHOCYTES
IMMUNE DEVIATION
CD27
JUVENILE IDIOPATHIC ARTHRITIS

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From the 2nd Division of Pediatrics, "G. Gaslini" Scientific Institute for Children, Genoa, Italy.

S. Chiesa, PhD; I. Prigione, PhD; F. Morandi, PhD; P. Bocca, Technician; V. Pistoia, MD, Head, Laboratory of Oncology; M. Gattorno, MD; A. Buoncompagni, MD; P. Picco, MD; A. Martini, Professor of Pediatrics, University of Genoa.

Address reprint requests to Dr. M. Gattorno, 2nd Division of Pediatrics, G. Gaslini Scientific Institute for Children, Largo G. Gaslini 5, 16147 Genoa, Italy. E-mail: marcogattorno@ospedale-gaslini.ge.it

Submitted July 22, 2003; revision accepted April 7, 2004.

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