PHENOTYPIC AND FUNCTIONAL DIFFERENTIATION OF SYNOVIAL MEMORY T CELLS IN JIA

Pediatric Rheumatology Online Journal → June 2003 → Epidemiology, Classification, Immunology and Immunogenetics → Abstract #9

M. Gattorno,¹ I. Prigione,² A. Gregorio,¹ S. Chiesa,² S. Gregorio,³ F. Morandi,² C. Gambini,⁴ V. Pistoia,² A. Martini.¹

¹Rheumatology Unit, IRCCS G. Gaslini; ²Laboratory of Oncology; ³1st Dept. of Orthopedics; ⁴Dept.of Pathology, G. Gaslini Scientific Institute, Genoa, Italy

Objective. To investigate the differential role of CCR7 and CCR5 in the synovial recruitment of memory T cells in JIA.
Patients and methods. Freshly isolated peripheral blood (PB) and synovial fluid (SF) lymphocytes from 10 JIA patients were studied for the expression of CCR7, CD45R0⁺, CD4⁺ by flow-cytometry. Expression of CCR5 and IFN-γ was next investigated on SF CD4⁺CCR7⁺ and CCR7^- memory T cells after negative selection of CD45RA cells. Synovial tissue (ST) from 3 JIA patients were also evaluated by for the expression of CCR5, CCR7 and its ligands CCL21 and CCL19.
Results. A higher absolute percentage of both CD4⁺CD45RO⁺CCR7⁺ and CD4⁺CD45RO⁺CCR7^-was found in SF compared to PBL (p = 0.04 and p=0.005, respectively). However, gating on CD4⁺CD45RO⁺ cells, a significantly lower percentage of CCR7⁺ cells (median 41.2%, range 12-59%) was found in SF than in PB (median 65.5%, range 50-98%; p = 0.005). Thus, a prevalent enrichment of CCR7^- memory T cells in SF was shown. SF CD4⁺CCR7^- memory T cells displayed higher expression of CCR5 (median 85%, range 74-99%) and IFN Γ (median 27%, range 15-46), when compared to paired CCR7⁺ cells (65%, range 46-84%; p = 0.007; 40%; 24-69%, p = 0.04, respectively). At immunohistochemistry, CCR7⁺ lymphocytes were found in the deep perivascular infiltrate of synovial sublining layer, whereas CCR5⁺ cells were spread in the context of ST, thought the lining layer . Both CCL19 and CCL21 were expressed on the endothelial cells, especially in areas with a consistent perivascular lymphocytic infiltrate.
Conclusions. CCR7 may play a role in the synovial recruitment of memory T cells in the JIA. However, CD4⁺CD45RO⁺CCR7^- T cells with effector characteristics are the prevalent synovial subpopulation. Immunohistochemestry data may lead to postulate a differentiation of memory T cells in the synovial tissue. These issues seem to be consistent with the lymphoid-like structure of the inflamed synovium during chronic arthritides.