ABSTRACT
INTRODUCTION: Regulatory T or Treg cells, balance the peripheral immune response to allergens in allergic rhinitis. Traditionally, Treg (CD25+ Treg) is identified by the coexpression of Foxp3 and CD25, but this strategy does not represent the true inhibitory function of Treg cells. Helios has been thought of as novel marker of activated Tregs, with an important inhibitory function. Consequently, Helios was proposed as a marker of Treg. Recent articles have shown that Foxp3 and Helios co-expression (Helios+Tregs) is an important functional stage of Treg. OBJECTIVE: To compare the prevalence of CD25+Tregs and Helios+Tregs using a mouse model of allergic rhinitis. METHODS: Twenty mice were randomized into two groups. The test group comprised 10 allergic rhinitis model mice exposed to ovalbumin; the control group was exposed to saline. The fractions of CD25+Tregs, Helios+Tregs, Helios+CD25+, and Helios+Foxp3+CD25+Tregs present in the two groups were determined using flow cytometry. RESULTS: CD25+Tregs and Helios+Tregs were less abundant in the spleen and nasal mucosa cells of the allergic rhinitis model compared with the control. We also observed fewer Helios+Tregs than CD25+Tregs in nasal mucosa and splenic cells of both control and test groups. Moreover, we observed fewer Helios+Foxp3+, Helios+CD25+, and Helios+Foxp3+CD25+ Tregs in the nasal mucosa in the allergic rhinitis model. Helios was expressed the most in CD4+ CD25+Foxp3+ T-cells, followed by CD4+ CD25-Foxp3- T-cells. Approximately 75% of CD25+Tregs were Helios+ in spleens of allergic rhinitis and control mice. CONCLUSION: This is the first report of the proportions of Helios+Tregs in nasal mucosa and spleens of allergic rhinitis mice. Gating true inhibitory Tregs with the coexpression of Foxp3 and Helios might be more useful than relying on the expression of CD25. This study provides a new insight for Treg studies of allergic rhinitis, and the potential utility of the marker as a therapeutic target.
Subject(s)
Forkhead Transcription Factors , Rhinitis, Allergic , Animals , Disease Models, Animal , Mice , Nasal Mucosa , T-Lymphocytes, RegulatoryABSTRACT
BACKGROUND: Regulatory CD4+ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-ß is a key regulator of Treg development and function. OBJECTIVE: The objective of this study is to determine whether the expression of functionally relevant TGF-ß-regulated molecules is altered in Tregs from patients with MS. METHODS: Expression of nine Treg markers was analyzed by multi-color flow cytometry in CD4+ T cells and Treg subpopulations of 31 untreated MS patients and age- and sex-matched healthy donors (HDs). Correlations between Treg marker expression and clinical variables were sought. RESULTS: Expression of the transcription factor Helios, which defines thymic-derived Tregs, was decreased in this Treg subpopulation. The frequency of peripherally generated Tregs was increased in patients with MS, particularly in patients with progressive MS. Low frequencies of thymic-derived Tregs were associated with magnetic resonance imaging (MRI) lesion-burden and a high relapse rate. Four surface markers associated with TGF-ß signaling (ABCA1, BTLA, DNAM-1, and GARP) were differentially expressed on Tregs from patients with MS and HDs. Expression levels of CD73, CD103, ABCA1, and PAR2 showed strong correlations with disease severity. CONCLUSION: We have identified novel markers abnormally expressed on Tregs from patients with MS that could detect patients with severe disease.
Subject(s)
Multiple Sclerosis , T-Lymphocytes, Regulatory , Cells, Cultured , Flow Cytometry , Gene Expression Regulation , HumansABSTRACT
A method to identify the three cryptic species of Protesilaus, (Lepidoptera: Papilionidae) from southern Brazil, based on genital morphology. I describe the male genital structures of three species of butterflies from Rio Grande do Sul, Brazil. Their external patterns do not differ enough to determine one species from another. All inhabit the same areas at the same time of the year. In an attempt to find a constant difference among them, as well as to establish the range of variability in each species, series of butterflies from different localities were dissected. The diagnostic structures found in all three species were named and drawn for their identification. Color patterns, width, separateness and presence or absence of the black bands and the color of the frons are not useful for recognizing P. nigricornis from P. stenodesmus or P. helios. The species group studied shows major morphological variability. For that reason, species level identification can be extremely difficult, particularly if the specimens are deteriorated. In conclusion, the only reliable way to correctly identify this species is by dissection of male genitalia. Rev. Biol. Trop. 55 (2): 665-671. Epub 2007 June, 29.
Analizo la estructura genital de los machos de tres especies de Protesilaus de Río Grande du Sul en Brasil, debido a que los caracteres morfológicos externos no proporcionan la información suficiente para identificarlas hasta el nivel de especie. Las tres especies se pueden encontrar en zonas de simpatría y en los mismos meses del año. Se nombraron y dibujaron las estructuras diagnósticas para cada una de las especies. Características morfológicas externas como el grosor, separación y presencia o ausencia de las bandas negras, y los colores en la cabeza, no son útiles para separar a P. nigricornis de P. stenodesmus y de P. helios. El grupo presenta una alta variabilidad morfológica, por lo que identificarlas a nivel de especie puede resultar difícil, principalmente si los especímenes se encuentran deteriorados. La identificación confiable se debe realizar mediante el estudio de los órganos genitales de los machos.