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The article presents a study which examines the reduction of newly produced T and B lymphocytes and T-cell receptor repertoire (TCR) diversity in the peripheral blood of multiple sclerosis (MS) patients treated with fingolimod. The study is investigated by real-time polymerase chain reaction (PCR), immune phenotyping, and spectratyping. Results show that newly produced T and B lymphocytes were reduced while T-cell repertoire increased after 12 months of treatment.

Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the ‘central memory-like’ Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy.Conclusions: The selective increase of ‘central memory-like’ subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy. [ABSTRACT FROM AUTHOR]

Purpose of the study Although HIV infection impacts the proportion and phenotype of regulatory T-cells (Tregs), discrepant results have been reported depending on the surface markers employed to characterize them and on the patient populations. In addition, the effects of a long-term combined antiretroviral therapy (cART) on Treg cells have not been thoroughly documented. Our study investigated the frequency and number of Tregs and their phenotype in two different groups of HIV-infected patients: one aviremic undergoing long-term cART and one viremic naïve to cART showing a similar CD4+ cell count. Methods Thirty-six HIV+ patients with sustained suppression of plasma viremia (<37 copies/mL) on effective cART for more than 6 years and 22 HIV+patients naïve to cART and without clinical signs of opportunistic infections or tumors at the time of study (untreated group) were included in the study. Healthy donors (HD) were used as control. Flow cytometry on fresh whole blood was used to quantify total Tregs (defined as CD25+CD127low/-CD4+ cells) and the following Treg subsets: naïve (CD45RA+CCR7+) Tregs, central-memory like Tregs (CD45RA-CCR7+, TregCM), effector-memory like Tregs (CD45RA-CCR7−, TregEM) Statistical comparisons of the percentages and number of Tregs and Treg subpopulations were performed by ANOVA or Kruskal-Wallis test. Analysis of covariance was employed in order to adjust for the effect of the age. The Spearman's test was used to assess correlations. Summary of results In viremic untreated and aviremic long-term cART-treated patients the percentage and number of the total Treg cells were not different from those of HD. However, the analysis of Treg phenotype showed a marked redistribution of the Treg subpopulations: in the untreated viremic patients, both the percentage and number of the TregCM subset decreased compared to HD and cART-treated patients, whereas only the percentage of naïve Tregs increased. In particular, the percentage of TregCM was inversely correlated with the viral load (r=−0.51; p=0.016). Conclusions In our aviremic long-term cART-treated and viremic untreated patients, the total Treg cell population seems to be unaffected by HIV infection. However, our results showed that the analysis of the naïve and memory-like Treg subsets may provide a better understanding of the real contribution of Tregs in HIV disease and therapy. [ABSTRACT FROM AUTHOR]