Newly produced T and B lymphocytes and T-cell receptor repertoire diversity are reduced in peripheral blood of fingolimod-treated multiple sclerosis patients

Background: Fingolimod inhibits lymphocyte egress from lymphoid tissues, thus altering the composition of the peripheral lymphocyte pool of multiple sclerosis patients. Objective: The objective of this paper is to evaluate whether fingolimod determines a decrease of newly produced T- and B-lymphocytes in the blood and a reduction in the T-cell receptor repertoire diversity that may affect immune surveillance. Methods: Blood samples were obtained from multiple sclerosis patients before fingolimod therapy initiation and then after six and 12 months. Newly produced T and B lymphocytes were measured by quantifying T-cell receptor excision circles and K-deleting recombination excision circles by real-time PCR, while recent thymic emigrants, naive CD8+ lymphocytes, immature and naive B cells were determined by immune phenotyping. T-cell receptor repertoire was analyzed by complementarity determining region 3 spectratyping. Results: Newly produced T and B lymphocytes were significantly reduced in peripheral blood of fingolimod-treated patients. The decrease was particularly evident in the T-cell compartment. T-cell repertoire restrictions, already present before therapy, significantly increased after 12 months of treatment. Conclusions: These results do not have direct clinical implications but they may be useful for further understanding the mode of action of this immunotherapy for multiple sclerosis patients

Modulation of Regulatory T-cell Subsets in Very Long-term Treated Aviremic HIV(+) Patients and Untreated Viremic patients

Naïve, central- and effector-like memory regulatory T cells (Tregs) were evaluated in untreated and long-term antiretroviral-treated HIV+ patients that showed comparable CD4+ cell levels, while being, respectively, viremic and aviremic. In the untreated patients, the percentage of naïve-like Tregs was significantly increased to the detriment of central memory regulatory T cells. This redistribution of regulatory Treg subsets may contribute to explain the partially preserved CD4+ cell counts seen in these patients despite the ongoing viremia. On the contrary, in the long-term treated patients, the percentages of Treg subsets were similar to those of healthy donors, demonstrating a restored Treg homeostasis. The characterization of Treg subsets, rather than an evaluation of the total Treg population, may lead to a deeper understanding of the Treg role in HIV infection and therapy

Immunological biomarkers identifying natalizumab-treated multiple sclerosis patients at risk of progressive multifocal leukoencephalopathy

Natalizumab-induced progressive multifocal leukoencephalopathy (PML) appears to be unleashed by complex interactions between viral and immunological host factors leading the latent form of JC virus to become pathogenic. Positive anti–JC virus antibody status, prior use of immunosuppressants, and increasing duration of natalizumab treatment have been proposed as risk factors for PML in multiple sclerosis patients, but while they may help to identify the most appropriate patients for natalizumab, their use have some limitations. Therefore, a large body of studies is ongoing to identify alternative, reliable immunological markers capable to improve the safety and efficacy of therapy and to guide tailored clinical decision