Aberration of CCR7+ CD8+ memory T cells from patients with systemic lupus erythematosus: an inducer of T helper type 2 bias of CD4+ T cells

摘要

Chemokine receptors are important in the entry of leucocytes into the inflammatory sites of systemic lupus erythematosus (SLE). CCR7⁺ and CCR7⁻ memory T cells exert different functions in homing, cytokine production and cytotoxicity. To determine whether differential expression and functions of the CCR7 occur in SLE patients, we examined CCR3, CCR4, CCR5, CCR7 and CCR9 on CD4⁺ and CD8⁺ T cells from normal and SLE subjects. Flow cytometry, real-time quantitative reverse transcription polymerase chain reactions and Northern blotting were used to detect the expression of chemokine receptors and cytokines; a chemotaxis assay was used to detect their functions. CD4⁺ T-cell stimulation with syngeneic CCR7⁺ CD8⁺ CD45RO⁺ T cells and dendritic cells (including transwell chambers) was used to induce cytokine expression. We demonstrated that CCR7 was selectively, frequently and functionally expressed on CD8⁺ (94·8%) but not on CD4⁺ (16·1%) T cells from patients with active SLE, whereas this phenomenon was not seen in normal subjects and in those whose SLE was inactive. CCR7⁺ CD8⁺ CD45RO⁺ memory T cells from patients with active SLE, themselves T helper type 2 (Th2) biased, were inducers of Th2 bias in CD4⁺ T cells in a cell–cell contact manner in vitro, meanwhile, the cells from both normal subjects and those whose SLE was inactive drove CD4⁺ T cells into a regulatory T-cell-derived cytokine pattern. Our findings might provide new clues to understanding the functions of CCR7⁺ CD8⁺ CD45RO⁺‘central’ memory T cells in autoimmue diseases (such as SLE). We suggest that in the case of active SLE, CCR7⁺ central memory T cells were able to enter peripheral blood and inflammatory sites from secondary lymphoid organs, were continuously expressing CCR7, and interacted with dendritic cells and functioned as CCR7^–‘effector’ memory T cells, which were described in normal humans.