Recently, we revealed the importance of follicular helper T cells (T_FH) in the pathogenesis of primary Sjögren’s syndrome (pSS). In the present study, we focused on the site of the inflammation and determined the composition of lymphocyte infiltration in labial salivary gland (LSG) biopsies with special emphasis on T_FHand germinal center B cells. We selected tissue blocks obtained from ten patients at the time of disease onset. Detection of cell specific markers was performed with immunohistochemical and immunofluorescence stainings. We evaluated patients’ clinical and laboratory features retrospectively and assessed the relation between disease course and early histopathological findings. LSG biopsies were graded based on the extension and arrangement level of periductal inflammatory cell infiltrates. T_FHcell markers (CD84, PD-1, and Bcl-6) occurred predominantly in more organized structures with higher focus scores. The coexpression of CD3 and Bcl-6 markers clearly identified T_FHcells close to Bcl-6⁺B cells with the typical formation of germinal centers. Systemic features were developed later in the disease course only in patients with highly structured infiltrates and the presence of T_FHcells. Our observations suggest that the presence of T_FHcells in LSGs at the disease onset may predict a more pronounced clinical course of pSS.

Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren’s syndrome (pSS), the role of follicular T helper (T_FH) cells as efficient helpers in the survival and differentiation of B cells has emerged. Our aim was to investigate whether a change in the balance of circulating (c)T_FH subsets and follicular regulatory T (T_FR) cells could affect the distribution of B cells in pSS. Peripheral blood of 38 pSS patients and 27 healthy controls was assessed for the frequencies of cT_FH cell subsets, T_FR cells, and certain B cell subpopulations by multicolor flow cytometry. Serological parameters, including anti-SSA, anti-SSB autoantibodies, immunoglobulin, and immune complex titers were determined as part of the routine diagnostic evaluation. Patients with pSS showed a significant increase in activated cT_FH cell proportions, which was associated with serological results. Frequencies of cT_FH subsets were unchanged in pSS patients compared to healthy controls. The percentages and number of cT_FR cells exhibited a significant increase in autoantibody positive patients compared to patients with seronegative pSS. The proportions of transitional and naïve B cells were significantly increased, whereas subsets of memory B cells were significantly decreased and correlated with autoantibody production. Functional analysis revealed that the simultaneous blockade of cT_FH and B cell interaction with anti-IL-21 and anti-CD40 antibodies decreased the production of IgM and IgG. Imbalance in T_FH subsets and T_FR cells indicates an ongoing over-activated humoral immune response, which contributes to the characteristic serological manifestations and the pathogenesis of pSS.

Growing evidence indicates the pronounced effects of physical activity on immune functions, which may largely depend on the type of exercise, intensity, and duration. However, limited information is available regarding the effects of low-impact exercises, especially on the level of adaptive immune system. Our study aimed to investigate and compare the changes in a broad spectrum of lymphocyte subtypes after 14 weeks of aerobic-type total-body-shaping workouts (TBSW) and Pilates workouts (PW) among healthy individuals. We determined the percentages of peripheral natural killer cells and different T and B lymphocyte subtypes with flow cytometry. At the end of the exercise program, significant changes in naïve and memory lymphocyte ratios were observed in TBSW group. Percentages of naïve cytotoxic T (Tc) cells elevated, frequencies of memory Tc and T-helper cell subsets decreased, and distribution of naïve and memory B cells rearranged. Proportions of activated T cells also showed significant changes. Nonetheless, percentages of anti-inflammatory interleukin (IL)-10-producing regulatory type 1 cells and immunosuppressive CD4⁺CD127^lo/−CD25^bright T regulative cells decreased not only after TBSW but also after PW. Although weekly performed aerobic workouts may have a more pronounced impact on the adaptive immune system than low-impact exercises, both still affect immune regulation in healthy individuals.

Sarcopenia, defined as loss of muscle mass and strength, develops gradually with aging or after chronic disease. Efforts are ongoing to identify the best interventions that can slow down or stop sarcopenia. Nutrition-based interventions and exercise therapy may be beneficial; however, pharmacotherapy also could play a role. The effect of ACE inhibitors on physical performance is controversial. The present study investigates the impact of functional training on sarcopenia in the presence or absence of ACEi in elderly females. A total of 35 women over 65 years of age were selected for two groups on the basis that they were taking ACEi (n = 18) or not (n = 17). All subjects conducted a training program two times a week for 6 months. We examined various factors related to sarcopenia. After completing the short physical performance battery (SPPB) test, we found a significant improvement after 6 months of functional training. SPPB values of the ACEi group were significantly lower at the beginning of the study; however, we observed no difference between the SPPB results of the two groups after the training period. We conducted further studies to measure posture and spine mobility. Our Schober and Cobra test results revealed significantly improved spine mobility (both flexor and extensor) in both groups after 6 months of training. Furthermore, the grip strength of the hands, studied by an electric dynamometer, was significantly improved in both groups at the end of the training period. Our results indicated that functional training may improve body composition and muscle strength in patients diagnosed with sarcopenia. Furthermore, ACEi may be a helpful additional therapy in older adult patients suffering from severe sarcopenia.

Systemic lupus erythematosus (SLE) is characterized by the breakdown of self-tolerance, the production of high-affinity pathogenic autoantibodies and derailed B cell responses, which indicates the importance of central players, such as follicular T helper (T_FH) subsets and follicular T regulatory (T_FR) cells, in the pathomechanism of the disease. In this study, we aimed to analyze the distribution of the circulating counterparts of these cells and their association with disease characteristics and B cell disproportions in SLE. We found that the increased percentage of activated circulating T_FH (cT_FH) and cT_FR cells was more pronounced in cutaneous lupus; however, among cT_FH subsets, the frequency of cT_FH17 cells was decreased in patients with lupus nephritis. Furthermore, the decreased proportion of cT_FH17 cells was associated with low complement C4 levels and high disease activity scores. We also investigated whether the blocking of the IL-21 receptor (IL-21R) with an anti-IL-21R monoclonal antibody inhibits the B cell response, since IL-21 primarily produced by T_FH cells potentially promotes humoral immunity. We observed that anti-IL-21R inhibited plasmablast generation and immunoglobulin production. Our study demonstrated that, besides cT_FR/cT_FH imbalance, cT_FH17 cells play a crucial role in SLE pathogenesis, and modulating cT_FH-B cell interaction through the IL-21/IL-21R pathway may be a promising therapeutic strategy to suppress the pathological B cell response.

Maternal B cells play a crucial role in the development and maintenance of pregnancy, due to their humoral activities and regulatory functions. In the study, we investigated the alterations in the distributions of naïve and memory B cell subsets, as well as regulatory B (Breg) cells, in the third trimester of pregnancy. Peripheral blood from 14 healthy pregnant women in the third trimester and 7 healthy non-pregnant women was collected and examined for the frequencies of B cell subsets, including IgD⁺CD27⁻ naïve, IgD⁺CD27⁺ un-switched memory, IgD⁻CD27⁺ switched memory, CD38^intCD24^int mature–naïve, CD38⁻CD24^hi primarily memory and CD38^hiCD24^hi transitional B cells by flow cytometry. Breg cell subsets were also characterized based on the expression of CD5, CD1d and IL-10. In pregnant women, the proportions of un-switched memory and transitional B cells were significantly decreased. Additionally, the frequencies of both CD5⁺CD1d⁺ Breg and IL-10-producing B10 cells were decreased in pregnancy. Changes in the distribution of transitional B cells as well as Breg cells may be crucial contributors for the development of altered maternal immune responses and tolerance needed for the maintenance of normal pregnancy in the third trimester.