To study the steps in the differentiation of human memory CD4 T cells, we characterized the functional and lineage relationships of three distinct memory CD4 subpopulations distinguished by their expression of the cysteine chemokine receptor CCR7 and the TNFR family member CD27. Using the combination of these phenotypic markers, three populations were defined: the CCR7+CD27+, the CCR7−CD27+, and the CCR7−CD27− population. In vitro stimulation led to a stepwise differentiation from naive to CCR7+CD27+ to CCR7−CD27+ to CCR7−CD27−. Telomere length in these subsets differed significantly (CCR7+CD27+ > CCR7−CD27+ > CCR7−CD27−), suggesting that these subsets constituted a differentiative pathway with progressive telomere shortening reflecting antecedent in vivo proliferation. The in vitro proliferative response of these populations declined, and their susceptibility to apoptosis increased progressively along this differentiation pathway. Cytokine secretion showed a differential functional capacity of these subsets. High production of IL-10 was only observed in CCR7+CD27+, whereas IFN-γ was produced by CCR7−CD27+ and to a slightly lesser extent by CCR7−CD27− T cells. IL-4 secretion was predominantly conducted by CCR7−CD27− memory CD4 T cells. Thus, by using both CCR7 and CD27, distinct maturational stages of CD4 memory T cells with different functional activities were defined.

Therefore we propose, from a serological point of view, to extend the mugwort-celery syndrome to the birch-mugwort-celery syndrome.

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Objective. The chemokine receptor CCR7 and the tumor necrosis factor receptor family member CD27 define 3 distinct, progressively more differentiated maturational stages of CD4 memory subpopulations in healthy individuals: the CCR7؉,CD27؉, the CCR7؊, CD27؉, and the CCR7؊,CD27؊ populations. The goal of this study was to examine maturational disturbances in CD4 T cell differentiation in systemic lupus erythematosus (SLE), using these phenotypic markers.Methods. Phenotypic analysis by flow cytometry, in vitro stimulation experiments, telomere length measurement, and determination of inducible telomerase were carried out.Results. In SLE patients, significant increases of CCR7؊,CD27؊ and CCR7؊,CD27؉ and a reduction of CCR7؉,CD27؉ CD4 memory T cells were found. In vitro stimulation of SLE T cells showed a stepwise differentiation from naive to CCR7؉,CD27؉ to CCR7؊,CD27؉ to CCR7؊,CD27؊; telomere length and inducible telomerase decreased in these subsets in the same progressive sequence. The in vitro proliferative response of these populations progressively declined as their susceptibility to apoptosis increased. Interestingly, a significant reduction in inducible telomerase was noted in SLE naive and CCR7؉,CD27؉ CD4؉ memory T cells. Additionally, SLE CCR7؊,CD27؉ and CCR7؊, CD27؊ CD4 memory T cells proliferated poorly in response to in vitro stimulation and underwent significantly more apoptosis than their normal counterparts. Finally, expression of CXCR4 was significantly reduced in all SLE subsets compared with normal. Conclusion.Together these data indicate an increased degree of in vivo T cell stimulation in SLE, resulting in the accumulation of terminally differentiated memory T cells with a decreased proliferative capacity and an increased tendency to undergo apoptosis upon stimulation.