B cells are required for sunlight protection of mice from a CNS-targeted autoimmune attack

The ultraviolet (UV) radiation contained in sunlight is a powerful immune suppressant. While exposure to UV is associated with protection from the development of autoimmune diseases, particularly multiple sclerosis, the precise mechanism by which UV achieves this protection is not currently well understood. Regulatory B cells play an important role in preventing autoimmunity and activation of B cells is a major way in which UV suppresses adaptive immune responses. Whether UV-protection from autoimmunity is mediated by the activation of regulatory B cells has never been considered before. When C57BL/6 mice were exposed to low, physiologically relevant doses of UV, a unique population of B cells was activated in the skin draining lymph nodes. As determined by flow cytometry, CD1d^lowCD5^–MHC-II^hiB220^hi UV-activated B cells expressed significantly higher levels of CD19, CD21/35, CD25, CD210 and CD268 as well as the co-stimulatory molecules CD80, CD86, CD274 and CD275. Experimental autoimmune encephalomyelitis (EAE) in mice immunized with MOG/CFA was reduced by exposure to UV. UV significantly inhibited demyelination and infiltration of inflammatory cells into the spinal cord. Consequently, UV-exposed groups showed elevated IL-10 levels in secondary lymphoid organs, delayed EAE onset, reduced peak EAE score and significantly suppressed overall disease incidence and burden. Importantly, protection from EAE could be adoptively transferred using B cells isolated from UV-exposed, but not unirradiated hosts. Indeed, UV-protection from EAE was dependent on UV activation of lymph node B cells because UV could not protect mice from EAE who were pharmacologically depleted of B cells using antibodies. Thus, UV maintenance of a pool of unique regulatory B cells in peripheral lymph nodes appears to be essential to prevent an autoimmune attack on the central nervous system.     

Induced regulatory T cells: mechanisms of conversion and suppressive potential

Thymus-derived, naturally occurring CD4(+) Forkhead Box P3(+) regulatory T cells (nTreg) have suppressive activity that is important for the establishment and maintenance of immune homeostasis in the healthy state. Abundant reports have demonstrated that they can suppress pathogenic processes in autoimmune diseases and inhibit transplant rejection and graft-versus-host disease. Far less is known about induced regulatory T cells (iTreg) that are generated from naive T cells in the periphery or in vitro by directing naive T cells to acquire suppressive function under the influence of transforming growth factor-β and other factors. In this review, we describe mechanisms by which naive T cells are thought to be converted into iTreg. We also discuss the suppressive potential of iTreg, particularly in comparison with their naturally occurring counterparts, focusing on those reports in which direct comparisons have been made. Based on current knowledge, we consider the rationale for using iTreg versus nTreg in clinical trials.     

Low-dose UVB radiation perturbs the functional expression of B7.1 and B7.2 co-stimulatory molecules on human Langerhans cells

In previous studies, we have shown that ultraviolet (UV) B radiation perturbs the APC function of Langerhans cells (LC) by interfering with as-yet unidentified co-stimulatory signals. Recently, B7.1 and B7.2 on APC were shown to deliver important co-stimulatory signals through interaction with their counterreceptors CD28 and CTLA-4 on T cells. To determine whether UVB affects the functional expression of B7.1 or B7.2 on LC, B7.1 and B7.2 expression was studied on human LC by multiparameter flow cytometry. Little, if any, B7.1 or B7.2 was detected on LC freshly isolated from skin. However, following 48 h of tissue culture, expression of both B7.1 and B7.2 were markedly up-regulated. To test whether these molecules were functional, primary mixed epidermal cell leukocyte reactions (MECLR) were performed. Blocking monoclonal antibody (mAb) to B7.1 or B7.2 both inhibited the MECLR, with anti-B7.2 being much more effective than anti-B7.1. UVB radiation dose-dependently (100–200 J/m²) suppressed the culture-induced up-regulation of B7.1 and B7.2 on LC. Since LC exposed to the same UVB flux (UVB-LC) failed to stimulate alloreactive T cells in a MECLR, we questioned whether this was related to their inability to provide B7 co-stimulation. Indeed, when effective B7-CD28 signaling was ascertained by adding submitogenic doses of exogenous anti-CD28 mAb to UVB-LC, the proliferative response of alloreactive T cells was restored. We conclude that the suppressive effects of low-dose UVB radiation on the APC function of LC are, at least in part, due to an inhibition of functional B7.1 and B7.2 expression.     

Hapten-specific tolerance induced by acute, low-dose ultraviolet B radiation of skin requires mast cell degranulation

The deleterious effects of ultraviolet B radiation (UVR) on cutaneous immunity are mediated in part by cytokines released from cutaneous cells following radiation exposure. On the one hand, TNF-alpha has been advocated as the primary mediator of failed contact hypersensitivity induction, and, on the other hand, IL-10 has been held responsible for tolerance. While keratinocytes exposed to UVR have been found to produce both TNF-alpha and IL-10, there is reason to question whether these major cellular constituents of the epidermis are the relevant source of immunomodulatory cytokines after UVR. Dermal mast cells also produce TNF-alpha and IL-10, and we have recently reported that mast cell-derived TNF-alpha is required for UVR-induced impairment of CH induction. In this study, we have examined whether mast cells are also a relevant source of IL-10 in UVR-dependent tolerance. We found that (a) UVR fails to induce tolerance in mast cell-deficient mice, and (b) that tolerance occurs if mast cells are triggered to degranulate after ligation of the IgE receptor. Both types of tolerance were neutralized with anti-IL-10 antibodies, are hapten specific, and are associated with regulatory lymphoid cells. We conclude that mast cells are required in UVR-induced tolerance and may be one of the major sources of IL-10 that mediates the tolerance induced by acute, low-dose UVR.     

B细胞免疫耐受缺陷与系统性红斑狼疮的最新研究进展

系统性红斑狼疮(SLE)是一种全身多器官受累的自身免疫性疾病.致病性自身抗体是该病的一个标志性特征,并且在引发SLE患者临床表现中发挥重要作用,这些自身抗体导致免疫复合物沉积在内脏器官而引起炎症及机体损伤.尽管SLE存在多种分子途径异常以及多种细胞类型调节异常,但B细胞在该疾病中发挥中心作用.最近研究认为,调节自身反应性B细胞存活、分化及活化的中枢与外周耐受机制在SLE患者中存在缺陷.因此了解B细胞免疫耐受缺陷与SLE的最新研究进展十分必要.     

TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells,which decreases in contact hypersensitivity

Certain B cells termed as “regulatory B cells” (Bregs) can suppress the ongoing immune responses and a splenic CD5⁺CD1d^hi Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5⁺CD1d^hi Bregs. In this study, we isolated splenocytes or splenic CD19⁺ B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5⁺CD1d^hi Bregs by flow cytometry. FasL expression in CD5⁺CD1d^hi B cells was rapidly increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40 combinations failed to stimulate FasL expression in CD5⁺CD1d^hi B cells although the IL-10 production was up-regulated in this subset. In addition, LPS and other B10-cell inducers increased the expression of surface molecules like CD86 and CD25, which are correlated to the regulatory functions of B cells. Furthermore, NF-κB and NF-AT inhibitors decreased the TLR4-activated FasL expression in CD5⁺CD1d^hi B cells. Then we sorted splenic CD5⁺CD1d^hi Bregs using flow cytometry and found that TLR4-activated CD5⁺CD1d^hi Bregs suppressed the proliferation of CFSE-labeled CD4⁺ T cells in vitro, which was partly blocked by anti-FasL antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL expression in splenic CD5⁺CD1d^hi B cells was decreased compared to the control group after TLR4 ligation. Our findings suggest that the regulatory function of CD5⁺CD1d^hi B cells could be partly mediated by Fas-FasL pathway and this FasL expressing CD5⁺CD1d^hi Bregs might participate in the regulation of inflammatory diseases.     

Evidence that ultraviolet B radiation induces tolerance and impairs induction of contact hypersensitivity by different mechanisms.

Tumour necrosis factor-alpha (TNF-alpha) and cis-urocanic acid (UCA) have recently been implicated in the process by which ultraviolet B radiation (UVB) impairs the induction of contact hypersensitivity when dinitrofluorobenzene (DNFB) is painted on UVB-exposed skin. The evidence supports the hypothesis that UVB radiation converts trans- to cis-UCA in the epidermis which in turn causes the epidermis of UVB-susceptible mice to produce/contain excessive local amounts of TNF-alpha. When hapten is painted on TNF-alpha- or UVB-treated skin, contact hypersensitivity fails to develop. As UVB radiation also induces hapten-specific tolerance and suppressor T cells when hapten is applied to UVB-exposed skin of UVB-susceptible strains of mice, we examined whether TNF-alpha and/or UVB-irradiated UCA (UV-UCA) might be similarly involved in the mechanism by which UVB induces tolerance. We report that intracutaneously-injected TNF-alpha and UV-UCA altered the cutaneous environment such that when DNFB was painted on the injected site, hapten-specific tolerance was induced and suppressor cells were generated. However, the tolerance induced by UVB radiation and the tolerance that followed intracutaneous injection of UV-UCA were not reversed by neutralizing anti-TNF-alpha antibodies. Moreover, UV-UCA and TNF-alpha-induced tolerance and suppressor cells in both UVB-susceptible (UVB-S) and UVB-resistant mice, whereas UVB radiation induced tolerance only in UVB-S mice. We conclude that the mechanism by which UVB radiation induces tolerance in mice is separate and distinct from the mechanism by which UVB radiation impairs contact hypersensitivity induction. Moreover, our data support the view that the generation of suppressor cells and the development of hapten-specific tolerance may be mechanistically distinct. The possible molecular and cellular mediators of UVB-induced tolerance are discussed.     

Dynamics and magnitude of virus-induced polyclonal B cell activation mediated by BCR-independent presentation of viral antigen

Hypergammaglobulinemia and production of autoantibodies occur during many viral infections, and studies have suggested that viral antigen‐presenting B cells may become polyclonally activated by CD4 T cells in vivo in the absence of viral engagement of the BCR. However, we have reported that CD4 cells in lymphocytic choriomengitis virus (LCMV)‐infected mice kill adoptively transferred B cells coated with LCMV class II peptides. We report here that most of the surviving naïve B cells presenting class II MHC peptides undergo an extensive differentiation process involving both proliferation and secretion of antibodies. Both events require CD4 cells and CD40/CD40L interactions but not MyD88‐dependent signaling within the B cells. B cells taken from immunologically tolerant donor LCMV‐carrier mice with high LCMV antigen load became activated following adoptive transfer into LCMV‐infected hosts, suggesting that B cells present sufficient antigen for this process during a viral infection. No division or activation of B cells was detected at all in virus‐infected hosts in the absence of cognate CD4 T cells and class II antigen. This approach, therefore, formally demonstrates and quantifies a virus‐induced polyclonal proliferation and differentiation of B cells, which, due to their high proportion, would mostly have BCR not specific for the virus.     

Modulation of immunity to Borrelia burgdorferi by ultraviolet irradiation: Differential effect on Th1 and Th2 immune responses

Ultraviolet B (UVB) radiation suppresses the delayed-type hypersensitivity (DTH) response to alloantigen by a mechanism involving interleukin (IL)-10. It has been hypothesized, based on this result, that UV irradiation shifts the immune response from a Th1 to a Th2 response. We tested this hypothesis using Borrelia burgdorferi (Bb) as an antigen under conditions where both DTH and antibody responses could be assessed. Mice were irradiated with a single dose of UV and then immunized with Bb in complete Freund's adjuvant (CFA). DTH was assessed by footpad challenge. At various time points thereafter, mice were bled, and the serum antibodies to Bb were quantitiated. Only IgG1, IgG2a, and IgG2b were produced in response to Bb. The IgG2a and IgG2b antibody responses, as well as the DTH response to Bb, showed UV dose-dependent reductions after UV irradiation. The primary IgG1 response to Bb was very low and was unaffected by UV irradiation; however, the IgG1 secondary response was elevated in UV-irradiated mice. Injection of anti-IL-10 antibody into UV-irradiated mice within 24 h after UV exposure restored the DTH response, as well as the IgG2a and IgG2b antibody responses. In addition, injecting recombinant murine IL-10 mimicked some of the effects of UV radiation. Our results support the hypothesis that in vivo, UV irradiation down-regulates Th1 immune responses, while leaving Th2 responses intact, and suggest that IL-10 is an important mediator of this effect.     

Regulation of B lymphocytes and plasma cells by innate immune mechanisms and stromal cells in rheumatoid arthritis

B cells mediate multiple functions that influence immune and inflammatory responses in rheumatoid arthritis. Production of a diverse array of autoantibodies can happen at different stages of the disease, and are important markers of disease outcome. In turn, the magnitude and quality of acquired humoral immune responses is strongly dependent on signals delivered by innate immune cells. Additionally, the milieu of cells and chemokines that constitute a niche for plasma cells rely strongly on signals provided by stromal cells at different anatomical locations and times. The chronic inflammatory state therefore importantly impacts the developing humoral immune response and its intensity and specificity. We focus this review on B cell biology and the role of the innate immune system in the development of autoimmunity in patients with rheumatoid arthritis.     

The relative contributions of B and T lymphocytes in the human peripheral blood mutagen test system as determined by cell survival,mitogenic stimulation,and induction of chromosome aberrations by radiation

Ficoll-Hypaque-separated subpopulations of human peripheral blood T and B lymphocytes were exposed to 0, 0.5, 1.0, 2.5, or 5.0 Gy of γ rays. Three parameters were examined: Survival, as measured by trypan blue dye exclusion in unstimulated cultures five days after irradiation; mitotic index, measured in phytohemagglutinin (PHA)-stimulated cultures 48 and 72 hours after irradiation; and chromosome aberration frequency, measured 48 or 60 hours after irradiation. Survival curves of T, B, and null cells are biphasic; the D₀ values for the radiosensitive populations of all three cell types are close to 0.6 Gy but are different for the radioresistant populations: 2.7 Gy for B cells, 4.77 Gy for T cells, and 6.03 Gy for null cells. B cells, as well as T cells, are stimulated to divide by PHA, and B cells comprise at least 10% of the mitotic figures seen in unirradiated cultures at 48 hours. The proportion of B lymphocytes in mitosis at any particular time after PHA stimulation decreases with increasing radiation dose, which reflects a higher mitotic radiosensitivity of B than of T cells. No significant difference, however, in chromosome aberration frequency was found between T and B cells.     

柯萨奇病毒B3 VP1蛋白、rAd/VP1和pcDNA3/VP1的免疫效果比较

目的 观察柯萨奇病毒B3(Coxsackievirus B3,CVB3)衣壳蛋白VP1、表达VP1蛋白的重组腺病毒rAd/VP1和重组质粒pcDNA3/VP1的免疫效果.方法 用原核细胞表达VP1蛋白并纯化、扩增重组腺病毒rAd/VP1,扩增并提取真核表达质粒pcDNA3/VP1.BALB/c小鼠随机分为4组,每组18只,分别在股四头肌注射VP1蛋白、rAd/VP1、pcDNA3/VP1和PBS.VP1蛋白组和pcDNA3/VP1组免疫3次,间隔3周;rAd/VP1组免疫2次,间隔2周.VP1蛋白、pcDNA3/VP1和rAd/VP1每次每只注射剂量分别为50μg、100μg和1.2×107PFU.用ELISA法和微量中和试验法检测各次免疫后血清CVB3特异性IgG抗体和中和抗体滴度;末次免疫后3周,CCK-8法检测脾脏淋巴细胞的CTL杀伤活性;用致死量CVB3攻击小鼠后,检测血中病毒滴度并观察动物的存活情况.结果 VP1蛋白组血清特异性IgG抗体和中和抗体滴度明显高于其他实验组(P＜0.05),而脾脏淋巴细胞CTL杀伤活性低于rAd/VP1组(P＜0.05);致死量病毒攻击后,VP1蛋白组血中病毒滴度低于pcDNA3/VP1和rAd/VP1组(P＜0.05),生存率明显高于这两组(P＜0.05).结论 VP1蛋白疫苗能诱导较高水平的体液免疫应答,对动物有明显的免疫保护作用,免疫效果优于质粒pcDNA3/VP1和重组腺病毒rAd/VP1.

Abstract：

Objective To compare the immune effects of Coxsackievirus B3 (CVB3) capsid protein VP1 expressed bacterially, recombinant adenovirus rAd/VP1 and recombinant plasmid pcDNA3/VP1which express VP1 protein in mice. Methods After expressed in prokaryotic cells, VP1 protein was purified. Recombinant adenovirus rAd/VP1 and recombinant plasmid pcDNA3/VP1 were amplified and extracted. Six to 8-week-old, male BALB/c mice were divided into four groups randomly. Each group contained 18 mice. The mice of pcDNA3/VP1 group or VP1 protein group were immunized intramuscularly with three injections at three weeks apart, of recombinant plasmid pcDNA3/VP1 at a dose of 100 μg/mouse or recombinant protein VP1 at a dose of 50 μg/mouse. The mice of rAd/VP1 group were immunized intramuscularly twice at two weeks interval with rAd/VP1 at a dose of 1.2 × 107 PFU. The control group was mock-immunized with 100 μl of PBS intramuscularly. Mice were bled from the retroorbital sinus plexus every two weeks after each immunization. ELISA and micro-neutralization test were used to detect levels of CVB3-specific IgG antibody and neutralizing antibody titers in the sera of immunized mice. Three weeks after the last immunization, the cytotoxic T lymphocyte(CTL) killing activity of spleen lymphocytes was detected with CCK-8 assay. Subsequently, virus titers in the sera of immunized mice were determined by the 50% cell culture infective dose( CCID50 ) assay on HeLa cell monolayers and percentage of animals surviving were observed after lethal CVB3 attack over a period of 21 days. Results The titers of specific IgG antibody and neutralizing antibody in sera of VP1 protein immunized mice were higher than other groups( P ＜0.05 ). While CTL killing activity of spleen lymphocytes of VP1 protein immunized mice was lower than mice in rAd/VP1 group( P ＜0. 05). Virus titers in sera of VP1 protein immunized mice were lower than the mice in pcDNA3/VP1 or rAd/VP1 groups ( P ＜ 0.05 ), while survival rate was significantly higher than these two groups ( P ＜ 0.05 ).Conclusion VP1 protein induced higher level of humoral immune response and acquired obvious immune protection effects in mice. The immunizing potency of VP1 protein vaccine surpassed plasmid pcDNA3/VP1or recombinant adenovirus rAd/VP1. It appeared to be a promising candidate among the three different vaccines.     

Kinetic study of TNF-alpha production and its regulatory mechanisms in acinar cells during acute pancreatitis induced by bile-pancreatic duct obstruction

Cytokines play a critical role in acute pancreatitis (AP) but the contribution of different cell sources to cytokine production is unclear. Unfortunately, there are no data concerning the molecular mechanisms involved in the inflammatory response in humans during AP. For this reason, the aim of this study was to analyse the ability of acinar cells, in comparison with leukocytes, to produce TNF-alpha at different stages of AP induced in rats by bile-pancreatic duct obstruction (BPDO) and to investigate the time course of oxidant-sensitive mechanisms involved in cytokine production. The role of oxygen free radicals as messengers of the mechanisms underlying acinar cell TNF-alpha production was assessed in BPDO rats treated with N-acetylcysteine (NAC). While monocytes were not able to produce TNF-alpha until 12 h after inducing AP, acinar cells triggered TNF-alpha production from 6 h after BPDO, at which time the pancreas develops maximal oxidative stress. Phosphorylated p38-MAPK and activated NF-kappaB were detected in acinar cells from 6 h after BPDO. NAC treatment reduced pancreatic glutathione depletion during the early stages of AP and attenuated the activation of p38-MAPK and NF-kappaB for 48 h following BPDO. As a result, acinar cells in NAC-treated rats failed to produce TNF-alpha during AP. In addition, NAC delayed monocyte TNF-alpha production, thereby maintaining low TNF-alpha levels in plasma during BPDO. In conclusion, acinar cells contribute directly to the inflammatory response during BPDO-induced AP by producing TNF-alpha even before inflammatory cells in the peripheral blood. The blockade of oxidant-mediated signal transduction pathways induced by NAC treatment prevented acinar cell TNF-alpha production.     

B lymphocyte life span,rate of division and differentiation are regulated by total cell number

I analyzed how B cell survival, the rate of B cell division and the rate of B cell activation may be affected in mice with different numbers of peripheral B cells. For this purpose, I created bone marrow (BM) chimeras with different BM B cell production; I analyzed peripheral B cell dynamics in these animals and studied the fate of carboxyfluorescein succinimidyl ester-labeled lymph node B cells transferred into these mice. I found that in lymphopenic mice, B cell life span is shortened and the rates of terminal B cell differentiation and cell death increased. As a consequence, I did not observe accumulation of B cells in mice with reduced but constant B-cell-poiesis. These results suggest that peripheral B cell survival relies not only on the number of competitors, as previously shown, but also on the rate of throughput of cells in a particular compartment.     

瑞舒伐他汀抑制JNK1/2的活化对急性心力衰竭大鼠心脏血流动力学、氧化应激及免疫应答的调节

目的:探究瑞舒伐他汀(RST)抑制JNK1/2的活化对急性心力衰竭(HF)大鼠心脏血流动力学、氧化应激及免疫应答的调节机制.方法:将100只雄性SD大鼠随机选取20只作为健康对照组(Control),80只制成急性HF模型后设为模型组(Cardiac failure)、低浓度RST组(2.5 mg/kg)、中浓度RST...     

Pregnancy-induced alterations of B cell maturation and survival are differentially affected by Fas and Bcl-2, independently of BcR expression

In the present work, we have analyzed the roles of two molecules involved in the regulation of cell survival, Bcl2 and Fas, in the pregnancy-induced down-regulation of B lymphopoiesis in mice. Our results show that the overexpression of the anti-apoptotic molecule Bcl2 in Bcl2-transgenic (Tg) B cells is able to protect 'D' fraction pre-B cells from pregnancy-induced deletion. In contrast, in Fas(lpr/lpr) mice bearing a mutated cell death receptor Fas, such B cell targets are not protected. Moreover, bone marrow B cell sub-populations at both ends of the differentiation pathway, i.e. pre-pro 'A' and mature 'E-F' fraction B cells, which are not the major targets of the pregnancy-induced down-regulation, are doubled during pregnancy in Fas(lpr/lpr) mice only. Altogether, these data strongly suggest that B cell down-regulation during pregnancy is due to apoptotic events blocked by Bcl2, but does not depend on a functional Fas receptor. The expression of a transgenic BcR in the 3-83mudelta BcR-Tg mouse model yields similar observations, which indicates that early BcR expression does not alter bone marrow B cell fates during pregnancy.     

慢性乙型肝炎患者、HBV携带者及急性自限性HBV感染者外周血调节性T细胞的差异及意义

目的比较慢性乙型肝炎患者、HBV携带者、急性自限性HBV感染者与正常对照之间外周血调节性T细胞（Treg）比例的差异，分析HBV感染后不同临床转归与Treg的关系，为慢性乙型肝炎的治疗提供新的线索。方法选取2004年2月至10月在我院肝炎门诊就诊的慢性乙型肝炎患者28例、HBV携带者23例、急性自限性HBV感染者19例以及健康献血员14例，使用流式细胞仪检测其外周血Treg的比例，分析其差异及临床意义。结果慢性乙型肝炎组外周血Treg占CD4^＋T细胞的比例为7．2％±3．1％，较HBV携带者组、急性自限性HBV感染者组及正常对照组增高；而HBV携带者组、急性自限性HBV感染者组及正常对照组之间Treg比例差异无统计学意义。结论Treg在HBV感染后慢性化的过程中可能发挥了一定的作用。     

Studies on delayed systemic effects of ultraviolet B radiation on the induction of contact hypersensitivity, 3. Dendritic cells from secondary lymphoid organs are deficient in interleukin-12 production and capacity to promote activation and differentiation of T helper type 1 cells

Ultraviolet-B radiation (UVR) of mouse skin promotes both local and systemic immune aberrations that are thought to be important in the pathogenesis of cutaneous malignancies. Acute, low-dose UVR regimens inhibit the induction of contact hypersensitivity (CH) in genetically susceptible mice by TNF-alpha-dependent mechanisms. In addition, these regimens also promote the development of tolerance when hapten is applied to the UVR-exposed site at the completion of the radiation treatment protocol. A third immune abnormality is also observed in mice exposed to acute, low-dose UVR. This abnormality, which develops within 48-72 hr of the completion of the UVR regimen, has been described among antigen-presenting cells within secondary lymphoid organs, including lymph nodes that do not drain the site of irradiation. Dendritic cells (DCs) from lymph nodes and spleens of mice exposed to UVR lack the capacity to induce CH if they are derivatized with hapten and injected intracutaneously into naive mice. The DC defect is related to the production of and systemic dissemination of interleukin-10 (IL-10) by keratinocytes within the epidermis of the UVR-exposed skin. We have now examined the nature of the functional aberration that exists among DCs within the secondary lymphoid organs of UVR-exposed mice by examining the capacity of DCs to express co-stimulatory molecules, and their ability to activate ovalbumin (OVA) -specific DO11.10 T-cell receptor transgenic T cells in vitro. Our results indicate that DCs from UVR-exposed mice produced insufficient amounts of IL-12. When pulsed with OVA, these cells were capable of inducing proliferation among DO11.10 T cells in vitro, but the responding cells produced neither IFN-gamma nor IL-10 and IL-4. A similar antigen-presenting cell defect was generated in mice treated with a subcutaneous injection of IL-10. We conclude that acute, low-dose UVR creates an IL-10-dependent functional deficit in DCs in secondary lymphoid organs, and that this defect robs UVR-exposed mice of the capacity to develop CH when hapten is painted epicutaneously.