Regulatory T Cells Phenotype in Different Clinical Forms of Chagas' Disease

CD25High CD4+ regulatory T cells (Treg cells) have been described as key players in immune regulation, preventing infection-induced immune pathology and limiting collateral tissue damage caused by vigorous anti-parasite immune response. In this review, we summarize data obtained by the investigation of Treg cells in different clinical forms of Chagas' disease. Ex vivo immunophenotyping of whole blood, as well as after stimulation with Trypanosoma cruzi antigens, demonstrated that individuals in the indeterminate (IND) clinical form of the disease have a higher frequency of Treg cells, suggesting that an expansion of those cells could be beneficial, possibly by limiting strong cytotoxic activity and tissue damage. Additional analysis demonstrated an activated status of Treg cells based on low expression of CD62L and high expression of CD40L, CD69, and CD54 by cells from all chagasic patients after T. cruzi antigenic stimulation. Moreover, there was an increase in the frequency of the population of Foxp3+ CD25HighCD4+ cells that was also IL-10+ in the IND group, whereas in the cardiac (CARD) group, there was an increase in the percentage of Foxp3+ CD25High CD4+ cells that expressed CTLA-4. These data suggest that IL-10 produced by Treg cells is effective in controlling disease development in IND patients. However, in CARD patients, the same regulatory mechanism, mediated by IL-10 and CTLA-4 expression is unlikely to be sufficient to control the progression of the disease. These data suggest that Treg cells may play an important role in controlling the immune response in Chagas' disease and the balance between regulatory and effector T cells may be important for the progression and development of the disease. Additional detailed analysis of the mechanisms on how these cells are activated and exert their function will certainly give insights for the rational design of procedure to achieve the appropriate balance between protection and pathology during parasite infections

Farmacovigilância da Cloroquina em pacientes com malária por Plasmodium Vivax tratados com esquema básico

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Spatial luminance contrast sensitivity measured with transient VEP: comparison with psychophysics and evidence of multiple mechanisms. Investigative Ophthalmology and Visual

PURPOSE. To compare the spatial luminance contrast sensitivity function (CSF) obtained with transient visual evoked potentials (VEPs) with that obtained with psychophysical measurements. METHODS. The stimuli consisted of horizontal luminance gratings. In the VEP experiments, 0.4, 0.8, 2, 4, 8, and 10 cpd of spatial frequency were used, at 1 Hz square-wave contrastreversal mode. Eight to 10 Michelson contrasts were used at each spatial frequency. Contrast thresholds were estimated from extrapolation of contrast response functions. Psychophysical sensitivities were obtained with spatial gratings of 0.4, 0.8, 1, 2, 4, 6, 8, and 10 cpd and presented at 1 Hz square-wave contrast-reversal or stationary mode (dynamic and static presentation, respectively). CSF tuning was estimated by calculating the ratio between peak sensitivity and the sensitivity at 0.4 cpd. RESULTS. In all subjects tested (n ϭ 6), VEP contrast-response functions showed nonlinearities-namely, amplitude saturation and double-slope amplitude functions that occurred at low and medium-to-high spatial frequencies, respectively. Mean electrophysiological and psychophysical CSFs peaked at 2 cpd. CSF tuning for electrophysiology and dynamic and static psychophysics were, respectively, 1.08, 1.11, and 1.31. Correlation coefficients (r 2 ) between electrophysiological CSF and dynamic or static psychophysical CSF were, respectively, 0.81 and 0.45. CONCLUSIONS. Electrophysiological and psychophysical CSFs correlated more positively when temporal presentation was similar. Spatial frequencies higher than 2 cpd showed that at least two visual pathways sum their activities at high contrasts. At low contrast levels, the results suggest that the transient VEP is dominated by the magnocellular (M) pathway. (Invest Ophthalmol Vis Sci. 2007;48:3396 -3404) DOI:10.1167/iovs.07-0018 T he use of the visual evoked potential (VEP) to study the human spatial luminance contrast sensitivity started in the 1970s, when it was demonstrated that the steady state VEP amplitude decreases with stimulus log contrast after a straightline relationship. 1 Moreover, the steady state VEP was successfully used to derive the spatial luminance contrast sensitivity function (CSF) in humans. When compared with behavioral measurements, the electrophysiological CSF was similar to the psychophysical CSF. 1 It was also observed that at spatial frequencies between 1.5 and 3 cpd, the contrast response functions were describable by two regressions with different slopes. 1 Further studies in humans and nonhuman primates have reported such nonlinearity of the VEP amplitude as a function of the stimulus contrast 2-11 : either a straight-line relation for low contrasts followed by saturation at high contrasts or a double-slope straight-line relation such as those described earlier. Originally, it was proposed that these nonlinearities indicate the contribution of different retinal regions, 1 but more recent studies have suggested that the nonlinearities are related to different contrast sensitivity mechanisms from parallel visual pathways. 6,10 -12 In this study, we assessed the similarity of the spatial luminance CSF obtained with transient VEP, when compared with that obtained psychophysically with similar stimuli. We also analyzed whether transient VEP amplitudes can be related to visual parallel pathway sensitivities. The transient VEP can be used as an objective tool to study spatial luminance CSF. There was good agreement between the electrophysiological and psychophysical measurements obtained with the same temporal frequency. Our results suggest that the M pathway is the main source of the VEP amplitude, at least at low-luminance contrasts. Some of these results have been presented in abstract form (Souza et al. IOVS 2006;47:ARVO E-Abstract 5379). METHODS Subjects Six healthy adults (three men and three women; mean age, 21 Ϯ 2 years) were monocularly tested. For each subject, only the eye with smallest dioptric error was tested. All subjects had normal or corrected acuity to 20/20, which was assessed by measuring the eye's refractive state with an autorefractor/keratometer (Humphrey 599; Carl Zeiss Meditec, Dublin, CA). None of the participants reported previous ocular, neural, or systemic diseases that could affect the visual system. All procedures were performed according to the tenets of the Declaration of Helsinki and were approved by the Committe