Effects of various radiation doses on induced T-helper cell differentiation and related cytokine secretion.

Exposure to ionizing radiation often induces T helper (Th) cell differentiation, resulting in an imbalance of Th1 and Th2 cellular subtypes, which can affect the efficacy of cancer radiotherapy. The aim of this study was to analyze differential expression of Th1, Th2 and Th3/Type 1 regulatory T cell (Tr1) subtype-related genes and cytokines in mouse thymocytes after high- and low-dose systemic radiation, using functional classification gene arrays and Elisa assays, and to explore the molecular mechanisms underlying radiation's immune effects and their relationship with Th1/Th2 immunity. We found that expression of 8 genes was upregulated after LDR, while expression of 5 genes was downregulated. After HDR, 54 genes were upregulated and 3 genes were downregulated, including genes related to Th1, Th2 and Th3/Tr1 cellular subtypes, Th1/Th2-type immune response genes and transcription factor-related genes. In the foregoing results, LDR and HDR in the thymus induced opposite patterns of expression for Th1-, Th2- and Th3-type related cytokines TGF-ß, C/EBP-ß and TNF-α. We also found that expression of Interferon-γ (IFN-γ) and Interleukin-2 (IL-2), which have a moderating effect on immune function, was upregulated after LDR. Furthermore, the secretion of negative regulatory factors Interleukin-1ß (IL-1ß), Interleukin-4 (IL-4), transforming growth factor-ß (TGF-ß) and Interleukin-21 (IL-21) was reduced after LDR, but HDR produced the opposite effect and stimulated their expression. These findings suggest that LDR may induce a Th1-type immune response, while HDR may lead to a Th2-type immune response.

Tyndallized Lactobacillus plantarum HY7712 Restores Whole-Body γ-Irradiation-Impaired Th Cell Differentiation in Mice.

In the present study, we investigated the effect of tyndallized HY7712 (tHY7712) on the expression of Th cell specific transcription factors and cytokines in whole-body γ-irradiated mice. Oral administration of tHY7712 strongly recovered the γ-irradiation-suppressed expression of helper T (Th) cell- and regulatory T cell-related transcription factors and cytokines, such as T-bet, Foxp3, IFN-γ, TNF-α, and IL-10, and suppressed Th2 cell-associated transcription factor and cytokine GATA3 and IL-5, respectively. Furthermore, compared with the control, tHY7712 treatment also restored γ-irradiation-impaired natural killer and cytotoxic T cell activities against YAC-1 tumor cells to 97.8% and 98.6%, respectively.

Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses after exposure to ionizing radiation.

Dendritic cell function is modulated by stromal cells, including fibroblasts. Although poorly understood, the signals delivered through this crosstalk substantially alter dendritic cell biology. This is well illustrated with release of TNF-α/IL-1ß from activated dendritic cells, promoting PGE2 secretion from stromal fibroblasts. This instructs dendritic cells to up-regulate IL-23, a key Th17-polarizing cytokine. We previously showed that ionizing radiation inhibited IL-23 production by human dendritic cells in vitro. In the present study, we investigated the hypothesis that dendritic cell-fibroblast crosstalk overcomes the suppressive effect of ionizing radiation to support appropriately polarized Th17 responses. Radiation (1-6 Gy) markedly suppressed IL-23 secretion by activated dendritic cells (P < 0.0001) without adversely impacting their viability and consequently, inhibited the generation of Th17 responses. Cytokine suppression by ionizing radiation was selective, as there was no effect on IL-1ß, -6, -10, and -27 or TNF-α and only a modest (11%) decrease in IL-12p70 secretion. Coculture with fibroblasts augmented IL-23 secretion by irradiated dendritic cells and increased Th17 responses. Importantly, in contrast to dendritic cells, irradiated fibroblasts maintained their capacity to respond to TNF-α/IL-1ß and produce PGE2, thus providing the key intermediary signals for successful dendritic cell-fibroblasts crosstalk. In summary, stromal fibroblasts support Th17-polarizing cytokine production by dendritic cells that would otherwise be suppressed in an irradiated microenvironment. This has potential ramifications for understanding the immune response to local radiotherapy. These findings underscore the need to account for the impact of microenvironmental factors, including stromal cells, in understanding the control of immunity.

Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy.

BACKGROUND: Sonodynamic therapy (SDT) was developed as a localized ultrasound-activated cytotoxic therapy for cancer. The ability of SDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque, in which selective accumulation of the sonosensitizer, protoporphyrin IX (PpIX), had been demonstrated. Here we investigate the effects of PpIX-mediated SDT on macrophages, which are the main culprit in progression of atherosclerosis. METHODS AND RESULTS: Cultured THP-1 derived macrophages were incubated with PpIX. Fluorescence microscopy showed that the intracellular PpIX concentration increased with the concentration of PpIX in the incubation medium. MTT assay demonstrated that SDT with PpIX significantly decreased cell viability, and this effect increased with duration of ultrasound exposure and PpIX concentration. PpIX-mediated SDT induced both apoptosis and necrosis, and the maximum apoptosis to necrosis ratio was obtained after SDT with 20 µg/mL PpIX and five minutes of sonication. Production of intracellular singlet oxygen and secondary disruption of the cytoskeleton were also observed after SDT with PpIX. CONCLUSION: PpIX-mediated SDT had apoptotic effects on THP-1 macrophages via generation of intracellular singlet oxygen and disruption of the cytoskeleton. PpIX-mediated SDT may be a potential treatment to attenuate progression of atherosclerotic plaque.

T helper and regulatory T cell cytokine profile in active, stable and narrow band ultraviolet B treated generalized vitiligo.

BACKGROUND: Vitiligo is a T cell mediated autoimmune depigmenting disease. Altered cytokine concentrations have been suggested in the pathogenesis of vitiligo. METHODS: T helper and regulatory T cell cytokines (IL-2, IFN-γ, IL-10, IL-13, IL-17 and TGF-ß) have been estimated by ELISA and their clinical correlation was determined. The study had 3 groups: group I with 80 vitiligo patients (60 active and 20 stable), group II with 25 narrow band ultraviolet B treated vitiligo and group III with 70 healthy controls. RESULTS: Significant difference was found in the serum interleukin (IL)-10, IL-13, IL-17A and TGF-ß1 concentrations among 3 groups (P<0.05). In group I, serum IL-2, IL-17A concentrations were significantly increased and TGF-ß1 concentrations were decreased in active vitiligo compared to stable vitiligo (P<0.05). Concentrations of IL-2, IL-10 and IL-13 (rho=-0.307, rho=-0.407, rho=-0.351 and P<0.05; respectively) were negatively- and TGF-ß1 concentrations were positively-correlated (rho=0.799, P=0.001) with disease duration. Interleukin-13 concentrations were negatively- and serum TGF-ß1 concentrations were positively-correlated (rho=-0.326, rho=0.244 and P<0.05; respectively) with percentage of body surface area involvement. CONCLUSIONS: Increased concentrations of serum IL-10, IL-13, and IL-17A and decreased concentrations of TGF-ß1 suggested altered cell-mediated immunity that may facilitate the melanocyte cytotoxicity in vitiligo.

Gamma-irradiation reduces the allogenicity of donor corneas.

PURPOSE: To evaluate the utility and allogenicity of gamma-irradiated corneal allografts. METHODS: Corneal buttons were harvested from C57BL/6 mice and decellularized with gamma irradiation. Cell viability was assessed using TUNEL and viability/cytotoxicity assays. Orthotopic penetrating keratoplasty was performed using irradiated or nonirradiated (freshly excised) C57BL/6 donor grafts and BALB/c or C57BL/6 recipients. Graft opacity was assessed over an 8-week period and graft survival was evaluated using Kaplan-Meier survival curves. Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were performed to evaluate T-cell alloreactivity. Real-time PCR was used to investigate the corneal expression of potentially pathogenic T-helper 1, 2, and 17 cell-associated cytokines. RESULTS: Corneal cells were devitalized by gamma irradiation as evidenced by widespread cellular apoptosis and plasma membrane disruption. Nonirradiated allograft and isograft rates of survival were superior to irradiated allograft and isograft rates of survival (P < 0.001). Mixed lymphocyte reactions demonstrated that T-cells from irradiated allograft recipients did not exhibit a secondary alloimmune response (P < 0.001). Delayed-type hypersensitivity assays demonstrated that irradiated allografts did not elicit an alloreactive delayed-type hypersensitivity response in graft recipients (P ≤ 0.01). The corneal expression of T-helper 1, 2, and 17 cell-associated cytokines was significantly lower in failed irradiated allografts than rejected nonirradiated allografts (P ≤ 0.001). CONCLUSIONS: Gamma-irradiated corneas failed to remain optically clear following murine penetrating keratoplasty; however, gamma irradiation reduced the allogenicity of these corneas, potentially supporting their use in procedures such as anterior lamellar keratoplasty or keratoprosthesis implantation.

Quantitative assessment of regulatory proteins in blood as markers of radiation effects in the late period after occupational exposure.

The objective of this research was quantitative assessment of serum and membrane regulatory proteins in blood from nuclear workers as markers of radiation-induced alterations in immune homeostasis in the late period after protracted exposure of nuclear workers with different doses. The effector and regulatory lymphocytes were measured using a flow cytofluorometer in workers from the main facilities of the Mayak PA (aged ∼60 y up to 80 y) in the late period after combined exposure to external gamma-rays and internal alpha-radiation from incorporated 239Pu. The control group included non-occupationally exposed members of the Ozyorsk population matched by gender and age to the group of Mayak workers. Thirty serum proteins involved in regulation of immune homeostasis, such as growth factors, multifunctional interleukins, pro- and anti-inflammatory cytokines, and their receptors, were measured using ELISA in blood serum specimens from the Radiobiology Human Tissue Repository. The dosimetry estimates were obtained using Doses-2005. The correlation analysis revealed a statistically significant direct relationship of T-killers and plutonium body burden and a decreasing level of T-helpers with accumulated external dose in exposed individuals. There were differences in expression of membrane markers in young regulatory cells (double null T-lymphocytes, NKT-lymphocytes, regulatory T-cells, and an increase of activated forms of T-lymphocytes), which indicated an active role of regulatory cells in maintaining immune homeostasis in terms of protracted exposure. The assessment of regulatory proteins in blood indicated that growth factors (EGF, TGF-ß1, PDGF), multifunctional interleukins (IL-17A, IL-18), and pro-inflammatory cytokines (IL-1ß and INF-γ) could be potential markers of radiation-induced alterations in protein status. An imbalance of pro- and antiinflammatory proteins in blood and variations of protein profiles at the lower exposure levels (gamma-ray dose <1 Gy, plutonium body burden <0.74 kBq) in the late period after protracted exposure were less pronounced than at the higher exposure levels, which was probably explained by compensatory-adaptive responses in the late period among senile individuals with polypathology.

Low-dose gamma-rays and simulated solar particle event protons modify splenocyte gene and cytokine expression patterns.

The goal was to investigate the T helper (Th) response in splenocytes of mice exposed to low-dose/low-dose-rate (LDR) γ-rays, simulated solar particle event protons (sSPE), or combination of both. C57BL/6 mice were exposed to LDR γ-radiation ((57)Co) to a total dose of 0.05 Gray (Gy) at 0.024 cGy/h, either with or without subsequent exposure to 2 Gy sSPE protons. Expression of genes related to Th cells was evaluated immediately after exposure (day 0). On day 21, intra- and extracellular cytokine production was assessed after activation with anti-CD3 monoclonal antibodies (mAb) or phorbol 12-myristate 13-acetate/ionophore (PMA/I). Five genes were significantly modulated on day 0 in one or more of the irradiated groups compared to controls (p < 0.05): Ccl11, Ccr5, Cd80, Inha, and Il9. On day 21, numbers of cells positive for interferon-γ were high in the LDR + sSPE group versus 0 Gy and LDR γ-rays (p < 0.05), but there was no difference in IL-2 and TNF-α. Levels of secreted cytokines after anti-CD3 mAb activation were high for 5 (MIP-1α, GM-CSF, IFN-γ, TNF-α, IL-13) and low for 2 (IL-7, IL-9) in all irradiated groups. Priming with LDR photons had a significant effect on IFN-γ and IL-17 compared to sSPE protons alone; IL-2 was low only in the LDR + sSPE group. The cytokine patterns after anti-PMA/I activation were different compared to anti-CD3 mAb and with fewer differences among groups. The data show that total-body exposure to space-relevant radiation has profound effects on Th cell status and that priming with LDR γ-rays can in some cases modulate the response to sSPE.

UV-induced immunosuppression and the efficacy of vaccination.

Exposure to ultraviolet radiation (UVR) suppresses immunity by complex pathways, initiated by chromophores located in the skin and ending with the generation of specific subsets of T and B regulatory cells. The primary and memory (recall) immune response to a wide variety of antigens, including microorganisms, can be reduced by UVR, leading to the possibility that the efficacy of vaccination could be similarly reduced. A limited number of animal models of vaccination demonstrate that this may indeed be the case. The situation in human subjects has not been rigorously assessed but there are indications from a variety of sources that UVR adversely affects the immune responses to several vaccines. These studies are reviewed and the implications for vaccine administration discussed. As vaccination represents a major public health measure world-wide for the control of an increasing number of common infections, it is important to maximise its efficacy; therefore further evaluation of UVR in the context of vaccination is required and warranted.

Mast cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function.

The most prevalent cancer diagnosed in the world is sunlight-induced skin cancer. In addition to being a complete carcinogen, UV radiation, the causative agent of skin cancer, induces immune suppression. Because UV-induced immune suppression is a well-recognized risk factor for skin cancer induction, it is crucial to understand the mechanisms underlying UV-induced immune suppression. Mast cells, which have recently emerged as immune regulatory cells, are particularly important in UV-induced immune suppression. UV exposure does not induce immune suppression in mast cell-deficient mice. We report that UV irradiation blocks germinal center (GC) formation, Ab secretion, and T follicular helper (Tfh) cell function, in part by altering the expression of transcription factors BCL-6 and BLIMP-1. No suppression of GC formation, Tfh cell IL-21 expression, or Ab secretion was observed in UV-irradiated mast cell-deficient (Kit(W-sh/W-sh)) mice. When mast cell-deficient mice were reconstituted with wild type mast cells, immune suppression was restored. Reconstituting the mast cell-deficient mice with bone marrow-derived mast cells from IL-10-deficient mice failed to restore the ability of UV radiation to suppress GC formation. Our findings demonstrate a function for mast cells, suppression of Tfh cell production, GC formation, and Ab production in vivo.

[Study of frequency of TCR-mutant T-helper lymphocytes and level of immunocompetent cells with mFasL apoptosis marker under conditions of ionizing radiation].

Were investigated the parameters of apoptosis of immune cells, the cell subpopulation composition and frequency of TCR-mutant lymphocytes in the peripheral blood of persons exposed to radiation. Increased number of peripheral mFasL-positive mononuclear cells and the accumulation of TCR-mutant T lymphocytes in a wide range of doses were found in the patients. It is doubtless that the effect of ionizing radiation is accompanied by a simulation of Fas-ligand expression on the surface of peripheral mononuclear cells and modification of the activating signal to apoptosis through the molecule CD4, CD8, CD3. The results can be caused by proapoptotic effect of radiation.

Inhibition of T helper 2 chemokine production by narrowband ultraviolet B in cultured keratinocytes.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) has recently been used for the treatment of various skin disorders. Its effects on the production of cytokines and chemokines by keratinocytes are unknown. OBJECTIVES: To investigate the effect of NB-UVB on production of chemokines and proinflammatory cytokines by keratinocytes in comparison with broadband (BB)-UVB. METHODS: Normal human epidermal keratinocytes (or the human keratinocyte cell line HaCaT in some experiments) at semiconfluency were irradiated with NB-UVB at 10, 100, 500 or 1000 mJ cm(-2) or BB-UVB at 10 or 100 mJ cm(-2). The cultures were maintained in the presence or absence of interferon (IFN)-gamma at 200 U mL(-1). The 72-h culture supernatants were analysed by enzyme-linked immunosorbent assay to quantify T helper (Th)1 chemokines (IFN-inducible protein 10 and monokine induced by IFN-gamma), Th2 chemokines [macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC)] and proinflammatory cytokines [interleukin (IL)-1alpha and tumour necrosis factor (TNF)-alpha]. The expression of mRNA for these molecules was simultaneously assessed by reverse transcriptase-polymerase chain reaction. The culture supernatants were also tested for their chemotactic activity for Th1 and Th2 cells. The two UVB sources were compared on the basis of their minimal erythemal doses and clinically used doses. RESULTS: Although both NB-UVB and BB-UVB increased the production of IL-1alpha and TNF-alpha, the augmentative effect of NB-UVB was less than that of BB-UVB. Both wavelength ranges of UVB enhanced or had no effect on Th1 chemokine production, but suppressed the production of Th2 chemokines MDC and TARC. This was confirmed by chemotactic assay, which showed decreased chemotactic activity for Th2 cells by the culture supernatants from NB-UVB-irradiated keratinocytes. CONCLUSIONS: NB-UVB reduces the production of Th2 chemokines without excess production of proinflammatory cytokines, suggesting its therapeutic effectiveness on Th2-mediated skin disorders as well as its relative safety in clinical usage.

[Updated assessment of efficacy of dry air radon baths of different concentrations at the stage of medical rehabilitation of patients with bronchial asthma].

We studied effects of dry air radon baths (DARB) on bronchial hypersensitivity and serum levels of proinflammatory cytokines in patients with bronchial asthma (BA) with reference to the disease severity and radon therapy regimen. DARB with radon concentrations 40 nCi/l significantly raise the threshold of bronchial sensitivity to metacholine compared to control and DARB with radon concentration 20 nCi/l. The effect was the highest in patients with mild asthma. Comparison of serum levels of alpha- and gamma-interferons, tumor necrosis factor alpha, IL-2, IL-4 and IL-6 has shown that alpha radon radiation significantly increases serum gamma-interferon and reduces IL-4 concentration. These changes were more evident in the group with high radon content. Thus, radon therapy has immunomodulating activity.

Age-dependent effects of in vitro radiofrequency exposure (mobile phone) on CD95+ T helper human lymphocytes.

Recent studies on "nonthermal" effects of mobile phone radiofrequency (RF) suggest that RF can interact with cellular functions and molecular pathways. To study the possible RF effects on human lymphocyte activation, we analyzed CD25, CD95, CD28 molecules in unstimulated and stimulated CD4+ e CD8+ T cells in vitro. Peripheral blood mononuclear cells (PBMCs) from young and elderly donors were exposed or sham-exposed to RF (1,800 MHz, Specific Absorption Rate 2 W/kg) with or without mitogenic stimulation. No significant changes in the percentage of these cell subsets were found between exposed and sham-exposed lymphocytes in both young and elderly donors. Nevertheless, after RF exposure we observed a slight, but significant, downregulation of CD95 expression in stimulated CD4+ T lymphocytes from elderly, but not from young donors. This age-related result is noteworthy given the importance of a such molecule in regulation of the immune response.

Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors.

PURPOSE: The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors. MATERIALS AND METHODS: Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8. RESULTS: CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations. CONCLUSIONS: Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.

[Intravascular photohemotherapy in the complex prophylaxis of purulent-septic complications after coronary shunting]. / Vnutrisosudistaia fotogemoterapiia v kompleksnoi profilaktike gnoino-septicheskikh oslozhnenii posle koronarnogo shuntirovaniia.

The article presents results of treatment of 78 patients with the history of coronary bypass operations for ischemic heart disease. There were 48 patients with high risk factors of the development of pyo-septic complications. Among them there were 27 patients treated by complex postoperative therapy including intravascular photomodification of blood. The intravascular irradiation of blood was shown to have a positive influence upon the development of the early postoperative period in this category of patients. The immunomodulating effect was noted due to a greater amount of activated lymphocytes and T-helpers in blood. The positive dynamics of immunological indices were in correspondence with the data of the clinical state, pyo-inflammatory complications were not registered in this group of patients. Early (on the 3rd-5th days) inclusion of the intravascular irradiation of blood in the complex postoperative therapy is thought to be expedient for the patients with high risk of pyo-inflammatory complications.

[Effect of small doses of ionizing radiation on selected antioxidant and immunologic parameters in patients with cervical cancer]. / Vliianie malykh doz ioniziruiushchego izlucheniia na otdel'nye pokazateli antiokislitel'noi sistemy zashchity organizma i immunnyi status bol'nykh rakom sheiki matki.

We analyzed the indices of antioxidant and immune systems in 69 patients with cervical carcinoma T3NxMo at different stages of radiotherapy. Radiation doses of 10-20 Gy were followed by certain normalization of antioxidant enzyme levels, increased concentrations of vitamins E and A in immunocompetent blood cells and improved the penetration and elastic properties of formed cells. The dosage stimulated the activity of helper-inducing and cytotoxic T-cells. Such effects should be taken into account when working out regimens of complex treatment of locally-advanced cervical carcinoma which include cytostatic drugs and radiation.

Autoreactivity, backstimulation and reproducibility in a helper T lymphocyte precursor assay.

Helper T lymphocyte precursor (HTLp) frequencies determined by limiting dilution analysis (LDA) have a predictive value for alloreactivity in allogeneic bone marrow transplantation. Methodological problems in LDA include autoreactivity in the responder or stimulator cell populations and interleukin 2 (IL-2) production by the stimulator cells as a response to the responder cells (backstimulation). The extent and impact of these aspects for IL-2 production and HTLp frequency determination were studied by autologous and allogeneic mixed lymphocyte reactions with healthy volunteers and HTLp determinations from bone marrow transplantation donor/recipient pairs. We found that autoreactivity occurred in the unirradiated cells with a reproducible inter-individual variation. The immunogenicity of the stimulator cells was preserved after gamma irradiation with 50 Gy and the risks of autoreactivity and backstimulation were limited. Higher doses of irradiation decreased the immunogenicity. Immune reactions to antigens present in the serum supplement of the culture medium were seen with foetal calf serum and to a lesser extent with pooled human sera. This could be avoided by the use of autologous serum. We were unable to ensure satisfactory culture conditions in serum-free medium. The reproducibility of the HTLp frequency determinations was tested for intra- and inter-assay variation. The coefficients of variation were estimated as 24% and 35%, respectively. This was acceptable considering the range of the HTLp frequencies (1:10(2) to 1:10(7)). The influence of the extent of autoreactivity of the bone marrow donors was investigated in 28 HLA-identical sibling transplantations. We found no correlation between the autoreactivity of the donors and the HTLp frequencies. The extent of autoreactivity of the donor did not correlate with the clinical outcome in terms of acute graft-versus-host disease, treatment-related mortality, risk of relapse and overall survival. In spite of methodological difficulties and interference from autoreactivity and backstimulation, reproducible quantification of clinically significant alloreactivity can be attained.

T-cell responses to mitogens in atomic bomb survivors: a decreased capacity to produce interleukin 2 characterizes the T cells of heavily irradiated individuals.

Significant decreases in the fraction of lymphocytes that are CD4(+) and increases in serum levels of some classes of immunoglobulin have been reported to occur in atomic bomb (A-bomb) survivors and in victims of the Chernobyl nuclear plant accident. To investigate the long-term effects of nuclear radiation on cellular immunity in more detail, we used limiting dilution assays with peripheral blood mononuclear cell preparations to analyze the T-cell responses of 251 A-bomb survivors exposed to less than 0.005 Gy and 159 survivors exposed to more than 1.5 Gy. The percentages of CD2-positive cells that were capable of proliferating in response to phytohemagglutinin (PHA) in the presence of exogenous interleukin 2 (IL2) did not differ substantially between distally exposed and more heavily exposed survivors. The heavily exposed survivors appeared to possess fewer T cells that were capable of proliferating in response to concanavalin A (Con A) or of producing interleukin 2. Assuming that CD4 T cells were the ones primarily responsible for producing IL2 in response to Con A, we were able to estimate how many cells in any given CD4 T-cell population were actually producing IL2. The results indicated that peripheral blood samples from heavily exposed survivors contained significantly fewer IL2-producing CD4 T cells than did similar samples from distally exposed survivors, indicating that significant exposure to A-bomb radiation may have a long-lasting negative effect on the capacity of CD4 T-cell populations to produce IL2.

Lymphocyte alterations after prolonged sunlight exposure.

BACKGROUND: It has been suggested that prolonged exposure to sunlight may induce systemic or local immune alterations, which may facilitate the development of skin cancer and, perhaps, non-Hodgkin's lymphona. The effects of prolonged sunlight exposure on peripheral blood cells were studied. METHODS: Leukocytes and lymphocyte subpopulations of 12 volunteers aged 10-45 were investigated before and after a 3-week summer holiday in seaside resorts in Greece. Lymphocyte phenotypes were estimated using monoclonal antibodies and flow cytometry. RESULTS: There were no significant differences with respect to total numbers of T cells, T-helper/inducer, T-suppressor/cytotoxic, B cells or HLA-Dr+ cells. However, we have found evidence of lymphocyte stimulation, reflected in an increase in cells expressing the interleukin-2 receptor (IL-2R) and, more specifically, an increase in the T cells expressing IL-2R and HLA-Dr antigens. An increase in natural killer cells has also been noticed. CONCLUSIONS: These findings suggest that prolonged intense exposure to sunlight may be associated with immunostimulation, rather than immunosuppression.