Short-term changes in frequencies of circulating leukocytes associated with narrowband UVB phototherapy in people with clinically isolated syndrome.

Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). Low environmental exposure to UV radiation is implicated in risk of developing MS, and therefore, narrowband UVB phototherapy might delay progression to MS in people with CIS. Twenty individuals with CIS were recruited, and half were randomised to receive 24 sessions of narrowband UVB phototherapy over a period of 8 weeks. Here, the effects of narrowband UVB phototherapy on the frequencies of circulating immune cells and immunoglobulin levels after phototherapy are reported. Peripheral blood samples for all participants were collected at baseline, and 1, 2, 3, 6 and 12 months after enrolment. An extensive panel of leukocyte populations, including subsets of T cells, B cells, monocytes, dendritic cells, and natural killer cells were examined in phototherapy-treated and control participants, and immunoglobulin levels measured in serum. There were significant short-term increases in the frequency of naïve B cells, intermediate monocytes, and fraction III FoxP3+ T regulatory cells, and decreases in switched memory B cells and classical monocytes in phototherapy-treated individuals. Since B cells are increasingly targeted by MS therapies, the effects of narrowband UVB phototherapy in people with MS should be investigated further.

Changes in T-lymphocytes in lung cancer patients after hyperthermic intraperitoneal chemotherapy or radiotherapy.

We investigated dynamic changes in T-lymphocyte subsets after hyperthermic intraperitoneal chemotherapy (HIPEC) or radiotherapy using flow cytometry. A total of 1423 lung cancer patients admitted to our hospital between October 2012 and July 2015 were enrolled, and age-matched healthy individuals served as controls. Peripheral blood mononuclear cells (PBMCs) were purified using standard Ficoll density gradient centrifugation, based on which CD3+, CD4+, and CD8+ T-cells were isolated. A surface marker was identified by flow cytometry. Immunohistochemical analysis determined the distribution of the cells in the tumor mass or adjacent tissues. A total of 957 patients (male: 555; female: 402; median age: 49.3 years) with lung cancer who had received only HIPEC or radiotherapy were enrolled. The patients were followed-up until death. No statistical difference was noticed between the patients who had received chemotherapy compared with the baseline levels. A remarkable elevation was noticed in the CD3+ T-cells in the patients three months after radiotherapy (78.71 ± 9.36 vs 68.15 ± 9.65, P < 0.05). The level of CD8+ in the patients who had received chemotherapy or radiotherapy was remarkably elevated in the post-treatment period (P < 0.05). The CD3+ and CD8+ T-cells were mainly expressed in the cytoplasm rather than in the adjacent tissues. The expression of CD3+ and CD4+ was correlated to tumor infiltration and metastasis. Remarkable elevation was noticed in the CD3+ T-cells in the patients three months after radiotherapy. The expression of CD3+ and CD4+ was negatively correlated to tumor infiltration and metastasis in non-small-cell lung cancer patients.

Recovery Profiles of T-Cell Subsets Following Low-Dose Total Body Irradiation and Improvement With Cinnamon.

PURPOSE: Inefficient T-cell reconstitution from x-ray-induced immune damage reduces antitumor response. To understand the profile of T-cell reconstitution after irradiation will overcome the barrier of antitumor immunity. This study aimed to identify the recovery profile of T-cell subsets following x-ray irradiation and to highlight the role of cinnamon on efficient T-cell restoration postexposure in the antitumor response. METHODS AND MATERIALS: CD3(+), CD8(+), and CD4(+) T cells and Th1, Th2, Th17, and regulatory T (Treg) cells were evaluated at different time points after single low-dose total body irradiation (SLTBI) with or without cinnamon treatments. T-bet, GATA3, RORγt, and Foxp3 signaling specific for Th1, Th2, Th17, and Treg were also analyzed by RT-PCR assay. The effects of cinnamon on efficient T-cell subset reconstitution was confirmed in a lung melanoma model in irradiated mice. RESULTS: Reconstitution of CD4(+) T cells was delayed more than that of CD8(+) T cells in T-cell restoration after SLTBI. The production of IFNγ by Th1 or Tc1 cells was sharply decreased and was accompanied by reduced T-bet mRNA, even when total T-cell numbers had recovered; the frequencies of Th17 and Treg cells and their specific transcription factors (RORγt and Foxp3, respectively) were obviously increased. Irradiation-induced inefficient T-cell reconstitution impaired the antitumor capacities in the lung melanoma model. Pretreatment with cinnamon in irradiated mice accelerated the generation of Th1 and reduced the differentiation of Treg cells by activating T-bet and limiting transcriptions of Foxp3. Improvement resulting from cinnamon pretreatment on the efficient T-cell recovery profile from SLTBI promoted antitumor immunity in the lung melanoma model. CONCLUSIONS: T-cell reconstitution from SLTBI was characterized by impaired Th1 and elevated Th17 and Treg cells. Cinnamon effectively improved the imbalance of T-cell subsets by promoting the proliferation of Th1 and by suppressing expansions of Th17 and Tregs. The role of cinnamon in efficient T-cell reconstitution from SLTBI is effective in antitumor immunity.

Prevention effects of Schisandra polysaccharide on radiation-induced immune system dysfunction.

In this study, we investigate the efficacy of SP (Schisandra polysaccharide) in prevention of radiation-induced immune dysfunction and discussed the underlying mechanisms with a Bal/bc mouse model. The data demonstrated that SP could reverse the decreases in the number of white blood cells and lymphocytes in peripheral blood. In addition, the immunoglobulin G (IgG) and complement C3 in blood serum were all decreased after radiation and SP could restore this radiation disorder. Furthermore, SP could reverse the deregulation of CD3(+)CD4(+) and CD3(+)CD8(+) T cell subsets in peripheral blood and thymus of mice after radiotherapy. We also performed terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and Immunohistochemistry (IHC) to investigate the apoptosis and underlying mechanisms of SP in thymus. Data showed that radiation-induced apoptosis of thymocytes could be reversed by SP through inducing upregulation of Bcl-2 expression and downregulation of Fas and Bax levels. Furthermore, SP has no any side-effects on immunity of normal mice. In conclusion, our results indicated that SP could effectively prevent immune injury during radiotherapy by protecting the immune system. This valuable information should be of assistance in choosing a rational design for therapeutic interventions of prevention immune system damage in the radiation treatment.

Effects of magnetic induction hyperthermia and radiotherapy alone or combined on a murine 4T1 metastatic breast cancer model.

PURPOSE: The purpose of this study was to explore the effects of MIH and radiotherapy alone or combined on metastatic breast cancer and the underlying mechanisms. MATERIALS AND METHODS: A murine 4T1 metastatic breast cancer model was established and randomly assigned into four treatment groups: C (control), R (radiotherapy), MIH, and MIH+R. Tumour volume, lung metastasis, the expression of Bax and MMP-9, T cell subsets, serum cytokine levels, and mouse survival were evaluated. RESULTS: Group MIH + R showed significantly reduced tumour volume, lung metastasis, improved survival and increased Bax expression compared to group R or MIH (P<0.05). MMP-9 expression in the primary tumour tissue was significantly increased in group R compared to the other groups (P<0.05), which could be brought down by combined MIH treatment. Group MIH +R showed significantly higher CD4(+) T cell percentage as well as CD4(+)/CD8(+) cell ratio than group R (P<0.05). Group MIH+R showed significantly higher serum levels of TNF-α, IFN-γ and IL-2 than group R (P<0.05). CONCLUSIONS: MIH not only promotes the tumour-cell killing effect of radiotherapy through Bax-mediated cell death, but also improves cellular immunity in mice under radiotherapy and decreases the potential of radiotherapy to enhance MMP-9 expression, which leads to significant improvement in lung metastasis and overall survival of mice under combined treatment of MIH and R. This study is the first to have explored the effect of combined hyperthermia and radiotherapy on tumour metastasis and the underlying mechanisms. It provides insights into the application of MIH as an adjuvant to radiotherapy for metastatic breast cancer.

8-methoxypsoralen plus ultraviolet A therapy acts via inhibition of the IL-23/Th17 axis and induction of Foxp3+ regulatory T cells involving CTLA4 signaling in a psoriasis-like skin disorder.

To elucidate the molecular action of 8-methoxypsoralen plus UVA (PUVA), a standard dermatological therapy, we used K5.hTGF-beta1 transgenic mice exhibiting a skin phenotype and cytokine abnormalities with strong similarities to human psoriasis. We observed that impaired function of CD4+CD25+ regulatory T cells (Tregs) and increased cytokine levels of the IL-23/Th17 pathway were responsible for the psoriatic phenotype in this mouse model. Treatment of K5.hTGF-beta1 transgenic mice with PUVA suppressed the IL-23/Th17 pathway, Th1 milieu, as well as transcription factors STAT3 and orphan nuclear receptor RORgammat. PUVA induced the Th2 pathway and IL-10-producing CD4+CD25+Foxp3+Tregs with disease-suppressive activity that was abolished by anti-CTLA4 mAb treatment. These findings were paralleled by macroscopic and microscopic clearance of the diseased murine skin. Anti-IL-17 mAb treatment also diminished the psoriatic phenotype of the mice. This indicated that both induced Tregs involving CTLA4 signaling and inhibition of the IL-23/Th17 axis are central for the therapeutic action of PUVA.

The effects of light-emitting diode irradiation at 610 nm and 710 nm on murine T-cell subset populations.

OBJECTIVE: The aim of this study was to investigate the effects of light-emitting diode (LED) irradiation (radiant power, 0.047 mW; irradiation area, 1.13 cm(2)) at 610 nm and 710 nm on T-lymphocyte subset populations and cytokine expression using an in vivo rat model. BACKGROUND DATA: The proliferation of CD4+ T lymphocytes was induced by polychromatic visible polarized light at the range of 540-780 nm in a previous study, but the specific target wavelength for this effect has not yet been identified. METHODS: Before and after 4 weeks of LED phototherapy, whole blood samples were collected from 610 nm, 710 nm, and control groups. The percentages of CD4+ and CD8+ T lymphocyte populations were determined by flow cytometry. The transcript levels of representative cytokines of CD4+ T-cell (interleukin [IL]-4, interferon [IFN]gamma) and proinflammatory cytokines (IL-1beta, IL-6) were assessed with the reverse transcriptase-polymerase chain reaction. RESULTS: The population of CD4+ T cells increased significantly in 710 nm group on day 28 (p < 0.05), but it did not increase in the 610 nm or control group. The population of CD8+ T cells did not show any significant change after irradiation in all groups. The mRNA expression of IL-4 increased in both the 610 nm and 710 nm groups compared to the control group, but IFNgamma was not detected in any group. The transcripts of IL-1beta and IL-6 were slightly induced in the 710 nm group. CONCLUSION: The in vivo irradiation of 710 nm wavelength LED significantly increases the population of murine CD4+ T cells, which suggests that this new phototherapeutic regimen might be promising for CD4+ T lymphocyte-mediated immune modulation therapy.

Treatment of early stages of mycosis fungoides with narrowband ultraviolet B. A clinical, histological and molecular evaluation of results.

BACKGROUND: Narrowband ultraviolet B (UVB) phototherapy is increasingly used in mycosis fungoides (MF). OBJECTIVE: We report on the results obtained in a prospective series of early MF patients receiving this therapeutic regimen. METHODS: In total, 22 patients were treated. Therapeutic results were evaluated on clinical, histological and molecular levels. Patients were then submitted to a clinical follow-up. RESULTS: The cumulative number of treatments ranged from 22 to 48 (mean: 29). A complete clinical remission (CCR) was obtained in 18/22 patients, and a partial clinical remission in 4 cases. Complete or partial histological responses were achieved in 9/15 (all in CCR) and 4/15 patients, respectively. The molecular response was evaluated in 12 patients, and a disappearance of the dominant T cell clone in the skin was obtained in only 3 cases. After 4-48 months of follow-up (mean 20.1 months), 7/18 patients in CCR (39%) relapsed. CONCLUSION: Narrowband UVB phototherapy is a well-tolerated treatment of early-stage MF, and its efficiency is maximal in very early stages (Ia). Even though clinical results seem very similar to PUVA through indirect and tentative comparisons with historical series, relapses tend to occur earlier than with PUVA, especially when an incomplete histological or molecular response was achieved.

Immune activation and radioprotection by propolis.

In this study, we focused on immune stimulation by Propolis, and examined changes in the effect of irradiation after Propolis administration. We also examined the radioprotective effect of Propolis by observing its effect on the immune system. The effect of immune activation by Propolis was investigated by measuring the total immunoglobulin (Ig) G and IgM. The radioprotective effect of immune activation by Propolis was investigated by measuring the T-lymphocyte subsets in the peripheral blood of mice following whole body irradiation. Compared with the control group, the IgG was significantly reduced in the Propolis group, indicating that Propolis suppressed IgG production. ELISA revealed that the amount of IgM in mouse serum was significantly higher in the Propolis group as compared with the control group, indicating that Propolis increased IgM production. The number of CD4-positive cells was increased only in the Propolis group. Likewise, the number of CD4-positive cells increased by 81% in the Propolis with irradiation group compared with the irradiation group alone. Compared with the control group, the Propolis group increased CD8-positive cells. Compared with the irradiation alone group, CD8-positive cells were decreased by Propolis with irradiation group. Propolis activated macrophages to stimulate interferon (IFN)-gamma production in association with the secondary activation of T-lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after Propolis administration activated helper T-cells to proliferate. In addition, activated macrophages in association with the secondary T-lymphocyte activation increased IFN-gamma production and stimulated proliferation of cytotoxic T-cells and suppressor T-cells, indicating the activation of cell-mediated immune responses.

Ultraviolet-A1 phototherapy modulates Th1/Th2 and Tc1/Tc2 balance in patients with systemic lupus erythematosus.

OBJECTIVE: Ultraviolet-A1 (UVA1) phototherapy is effective for a variety of dermatological diseases. We examined the effectiveness and reliability of low-dose UVA1 phototherapy (60 kJ/m2/treatment) in patients suffering from systemic lupus erythematosus (SLE). We studied the changes in immunological parameters. METHODS: The patients received a 9-week course of phototherapy according to the following regimen: five times a week during the first 3 weeks, three times a week during the second 3 weeks and twice during the last 3 weeks. Among other things, we analysed the proportions of T helper 1 (Th1), Th2, T cytotoxic (Tc1) and Tc2 cell populations in the peripheral blood of patients by flow cytometric detection of intracytoplasmic interferon gamma (IFN-gamma) and interleukin 4 (IL-4). RESULTS: Our study showed the improvement of clinical symptoms determined by the subjective clinical disease activity scoring and the SLE Disease Activity Index (SLEDAI). By the end of UVA1 phototherapy, the mean value of SLEDAI had decreased from 7.2+/-5.6 to 0.9+/-1.8, which was significant (P = 0.005). Immunological investigations detected a decrease in the frequency of IFN-gamma-producing Th1 and Tc1 cells and a decrease in the Th1/Th2 and Tc1/Tc2 ratios after UVA1 therapy. CONCLUSION: According to the literature, IFN-gamma has a pathogenic role in the development of SLE. We observed a decreased proportion of IFN-gamma-secreting cells, which we think is presumably one of the beneficial effects of UVA1 therapy. On the basis of our study, UVA1 phototherapy does seem to be an effective adjuvant in the treatment of SLE patients.

Immunological correlates of seasonal fluctuations in mood and behavior and their relationship to phototherapy.

Immunological parameters were studied before and after phototherapy, with bright and dim light, in 38 individuals with a range of retrospectively reported seasonal changes in mood and behavior. There was a significant negative correlation between the degree of mood and behavioral difficulties in fall and winter (seasonality) and the total number of circulating natural killer cells. Changes in the numbers of circulating helper T cells correlated significantly with changes in mood following phototherapy. Moreover, mitogen-induced lymphocyte blastogenesis increased significantly after phototherapy, but there was no significant difference between the bright and dim light treatments. The results suggest that cellular immune function is associated with both seasonality and response to phototherapy.