FOXP3+CD25− Tumor Cells with Regulatory Function in Sézary Syndrome

Cutaneous T-cell lymphoma (CTCL) has been suggested by in vitro experiments to represent a malignant CD4+ T-cell proliferation with a regulatory T-cell (Treg) phenotype (CD4+CD25+FOXP3+). We investigated percentages of FOXP3+ and CD25+ cells in the blood of 15 Sézary, 14 mycosis fungoides (MF), and 10 psoriasis (Pso) patients and 20 normal healthy donors (NHDs). We found similar numbers of FOXP3+ cells in MF (10.4% of blood CD4+ cells) and Pso (11.1%) patients and NHDs (9.8%). In 8 of 15 (53%) Sézary patients, significantly reduced percentages of FOXP3+ cells were seen in blood (2.9%) and skin (10.4%). Interestingly, 6 of 15 (40%) Sézary patients showed significantly increased percentages of FOXP3+ cells (39.7% (blood), 20.3% (skin)); however, these cells did not express CD25. In these latter patients, clone-specific TCR-Vβ-chain antibodies were used to demonstrate that these FOXP3+CD25− cells were monoclonal CTCL tumor cells. FOXP3+CD25− CTCL tumor cells showed a highly demethylated status of the foxp3 gene locus similar to Treg cells, and they were functionally able to suppress IL-2 mRNA induction in TCR-stimulated conventional T cells. Thus, FOXP3+CD25− CTCL tumor cells with functional features of Treg cells define a subgroup of Sézary patients who might carry a different prognosis and might require differential treatment

Ácidos grasos como marcadores de las relaciones tróficas entre el sestón, el zooplancton crustáceo y el sifonóforo Nanomia cara en Georges Basin y el cañón Oceanographer (NO Atlántico)

[EN] Fatty acid concentrations expressed as percentages of total fatty acid pools in seston, stage V copepodites of Calanus finmarchicus, adults of the euphausiid Meganyctiphanes norvegica, and the physonect siphonophore Nanomia cara were used to elucidate trophic links in Georges Basin and Oceanographer Canyon in September 2003. Seston at both locations was refractory and comprised mainly of saturated fatty acids. Phytoplankton did not contribute significantly to the fatty acid composition of seston or higher trophic levels. Only four fatty acids, i.e. 14:0, 16:0, 16:1 (n–7) and 18:1 (n–7), were transferred from seston to C. finmarchicus or M. norvegica, which suggested weak trophic interactions. Fatty acids transferred from the two species of crustaceans to N. cara included the same four fatty acids, along with three polyunsaturated fatty acids found in relatively high concentrations in both crustaceans, i.e. 20:3 (n–6), 20:5 (n–3) and 22:6 (n–3). In addition, 18:1 (n–9), which occurred in relatively high concentrations only in M. norvegica, and 18:0 and 18:2 (n–6), which were found in low concentrations in both crustaceans, also appeared to be transferred to N. cara. Overall, fatty acid trophic markers proved useful for identifying trophic links to N. cara[ES] En este estudio se utilizaron las concentraciones de ácidos grasos (expresadas como porcentajes) para identificar posibles relaciones tróficas entre el seston, el estadio V (copepoditos) de Calanus finmarchicus, los adultos del eufáusido Meganyctiphanes norvegica, y el sifonóforo fisonecto Nanomia cara en Georges Basin y el cañón submarino Oceanographer durante Septiembre de 2003. En ambos lugares el seston era muy refractario y compuesto básicamente por ácidos grasos saturados. El fitoplancton no contribuyó de forma significativa a la composición de ácidos grasos del seston o de niveles tróficos superiores. Sólo cuatro ácidos grasos [14:0, 16:0, 16:1 (n–7) y 18:1 (n–7)] se transfirieron potencialmente del seston a C. finmarchicus o M. norvegica, lo que sugiere una débil conexión trófica entre estos eslabones de la cadena. Los ácidos grasos transferidos de las dos especies de zooplancton crustáceo a N. cara incluyen los mismos descritos más arriba y otros tres ácidos grasos poliinsaturados [20:3 (n–6), 20:5 (n–3) y 22:6 (n–3)] encontrados en concentraciones relativamente elevadas en ambos crustáceos. Además, tanto el 18:1 (n–9) (encontrado en elevadas concentraciones en M. norvegica) y los 18:0 y 18:2 (n–6) (encontrados en bajas concentraciones en ambas especies de crustáceos) se transfieren a N. cara. Los ácidos grasos demuestran ser una herramienta útil para identificar conexiones tróficas en N. caraA grant to MJY from the National Science Foundation (NSF-0002493), the European Project EUROGEL, and USDA CRIS Project FLA-FAS-03978 supported this workPeer reviewe

Intracerebral Human Regulatory T Cells: Analysis of CD4+CD25+FOXP3+ T Cells in Brain Lesions and Cerebrospinal Fluid of Multiple Sclerosis Patients

Impaired suppressive capacity of CD4+CD25+FOXP3+ regulatory T cells (Treg) from peripheral blood of patients with multiple sclerosis (MS) has been reported by multiple laboratories. It is, however, currently unresolved whether Treg dysfunction in MS patients is limited to reduced control of peripheral T cell activation since most studies analyzed peripheral blood samples only. Here, we assessed early active MS lesions in brain biopsies obtained from 16 patients with MS by FOXP3 immunohistochemistry. In addition, we used six-color flow cytometry to determine numbers of Treg by analysis of FOXP3/CD127 expression in peripheral blood and cerebrospinal fluid (CSF) of 17 treatment-naïve MS patients as well as quantities of apoptosis sensitive CD45ROhiCD95hi cells in circulating and CSF Treg subsets. Absolute numbers of FOXP3+ and CD4+ cells were rather low in MS brain lesions and Treg were not detectable in 30% of MS biopsies despite the presence of CD4+ cell infiltrates. In contrast, Treg were detectable in all CSF samples and Treg with a CD45ROhiCD95hi phenotype previously shown to be highly apoptosis sensitive were found to be enriched in the CSF compared to peripheral blood of MS patients. We suggest a hypothetical model of intracerebral elimination of Treg by CD95L-mediated apoptosis within the MS lesion