Attenuation of contact hypersensitivity by cell‐permeable heat shock protein 70 in BALB/c mouse model

 In contact hypersensitivity (CHS), multiple cells, inflammatory mediators and cytokines are known to be involved in the regulation of the immune response. Previously, we revealed the reactive oxygen species generation by 2, 4, 6‐trinitrobenzene sulphonic acid (TNBS) in vivo, followed by heat shock protein 70 (Hsp70) carbonylation and the exogenous antioxidant role of cell‐permeable Hsp70. Here, we demonstrate the role of Hsp70 using cell‐permeable Hsp70 in the mouse CHS model. Pretreatment of cell‐permeable Hsp70: (i) suppressed ear swelling; (ii) down‐regulated phosphorylated p38, but up‐regulated phosphorylated extracellular signal‐regulated kinase; (iii) increased population of CD4⁺CD25⁺Foxp3⁺ T cells; (iv) decreased secretion of tumor necrosis factor‐α (TNF‐α), IL‐12, interferon‐γ and IL‐2 and (v) but up‐regulated IL‐4 and transforming growth factor beta (TGF‐β) in the lymph nodes. In conclusion, cell‐permeable Hsp70 attenuates CHS through modulation of MAPK pathway and regulation of Th1, Th2 and regulatory T cells.     

CD4+ T cells producing interleukin (IL)‐17, IL‐22 and interferon‐γ are major effector T cells in nickel allergy

Background It has been suggested that interleukin (IL)‐17 and IL‐22 play important roles in the elicitation of human allergic contact dermatitis; however, the frequencies of T cell subtypes producing IL‐17 and IL‐22 in human allergic contact dermatitis are unknown. Objectives To determine the frequencies of CD4⁺, CD8⁺ and γδ T cells producing IL‐17, IL‐22 and interferon (IFN)‐γ in the blood and skin from nickel‐allergic patients. Patients/materials/methods Blood samples were collected from 14 patients and 17 controls, and analysed by flow cytometry. Biopsies were taken from 5 patients and 6 controls, and analysed by immunohistochemistry and flow cytometry of skin lymphocytes. Results We found an increased frequency of γδ T cells in the blood, but no differences in the distribution of cytokine‐producing CLA⁺ T cell subtypes in nickel‐allergic patients as compared with controls. In nickel‐allergic patients, there was massive cellular infiltration dominated by CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ in nickel‐challenged skin but not in vehicle‐challenged skin. Conclusion CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ are important effector cells in the eczematous reactions of nickel‐induced allergic contact dermatitis in humans.     

Characterization of the T cell response in allergic contact dermatitis caused by corticosteroids

Background Delayed allergic hypersensitivity reactions have classically been described as type IV reactions, which are caused by T cells; however, the respective roles of CD4⁺ and CD8⁺ cells are yet to be defined. A central role for CD8⁺ cytotoxic T cells as effector cells has been suggested. Objectives To determine the type of T cell involved in corticosteroid allergy. Methods We analysed the kinetics of T cell recruitment and the cytokine production profile in positive patch tests of 27 corticosteroid‐sensitized patients, as compared with control sites and control subjects. Skin biopsies, collected at 8, 24 and 48 hr following drug application, were embedded in paraffin for histological and immunohistological staining, and, in some cases, also deep‐frozen for gene expression analyses. Results CD3⁺ T cells were rapidly recruited in concert with the positivity of the patch test sites. High levels of interleukin (IL)‐4, IL‐5 and, to a lesser extent, interferon‐γ suggested that both Th2 and Th1 cytokines were implicated. IL‐4 was also produced by γδ T cell receptor (TCR) lymphocytes. Conclusions This study showed that, in allergic contact dermatitis caused by corticosteroids, the inflammatory infiltrate is composed of CD3⁺ T cells with a predominant Th2 cytokine profile, among which IL‐4 is also produced by γδ TCR lymphocytes.     

CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin‐10 production predominantly by regulatory B cells

Conflicting observations have been reported concerning the role of CD1d‐dependent natural killer T (NKT) cells in contact hypersensitivity (CHS), supporting either a disease‐promoting or downregulatory function. We studied the role of NKT cells in CHS by comparing the immune response in CD1d knockout (CD1d KO) and wild‐type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0.5% DNCB (w/v) on the ears fifteen days later. We demonstrate that CD1d KO mice, as compared with Wt littermates, have more pronounced infiltration of mononuclear cells in the skin (29.1% increase; P < 0.001), lower frequencies of interleukin‐10⁺ B cells (B_regs) in the spleen (53.2% decrease; P < 0.05) and peritoneal cavity (80.8% decrease; P < 0.05) and increased production of interferon‐γ (3‐fold; P < 0.05) after DNCB sensitisation and challenge, which suggests an important regulatory and protective role of CD1d‐dependent NKT cells in CHS in our model, at least in part via regulation of IL‐10 producing B_regs.     

Osteopontin deficiency affects imiquimod‐induced psoriasis‐like murine skin inflammation and lymphocyte distribution in skin,draining lymph nodes and spleen

Osteopontin (OPN) that enhances autoimmunity is expressed in psoriasis lesions; however, its functions in psoriatic inflammation are unknown. We investigated the role of OPN in OPN deficient mice (OPN?/?) by inducing psoriasis‐like inflammation through skin application of imiquimod (IMQ). OPN?/? mice treated with IMQ showed delayed onset ear swelling and attracted less inflammatory cells to the skin. IMQ‐induced lymph node swelling was reduced in the absence of OPN, and IMQ‐mediated expansion of B cells was inhibited. Further, reduction of CD4⁺ T‐cell numbers by IMQ in lymph nodes was suppressed in OPN?/? mice, with an increase in the CD4/CD8 ratio. A comparable pattern was found in spleen. Importantly, IMQ‐induced IL‐17 and IL‐4 expression by CD4⁺ lymph node T cells was reduced in OPN?/? mice. In conclusion, OPN may modulate psoriasis‐like inflammation through altering lymphocyte distribution in skin and draining lymph nodes and by inducing IL‐17 expression of inflammatory T cells.     

Regulation of nickel-induced T-cell responsiveness by CD4+CD25+ cells in contact allergic patients and healthy individuals

In this study, we investigated the capacity of CD4⁺CD25⁺ regulatory T cells to suppress nickel‐specific effector T cells, both in nickel‐allergic patients and healthy controls. CD4⁺ cells isolated from allergic patients showed an increased proliferative response to nickel, whereas CD4⁺ cells from negative controls did not respond to allergen. When CD4⁺CD25⁺ cells were depleted, nickel‐specific responsiveness was strongly increased both in allergic and in non‐allergic individuals, with the most pronounced effect in allergic patients. These regulatory T cells were anergic to nickel but inhibited nickel‐specific CD4⁺CD25^– effector T cells in coculture experiments. CD4⁺CD25⁺ cells from nickel‐allergic patients showed only a limited capacity to suppress effector T‐cell responsiveness, because an increased nickel reactivity could still be detected in these cocultures. None of the isolated CD4⁺CD25⁺ cells, either isolated from healthy controls or allergic patients, produced IL‐10 in response to nickel. Overall, these results support the view that CD4⁺CD25⁺ cells can control the activation of nickel‐specific effector T cells in non‐allergic individuals, whereas this regulatory capacity is impaired in allergic patients. To investigate the presence of allergen‐specific regulatory T cells in truly naïve, non‐sensitized individuals, T‐cell reactivity should also be studied with non‐environmental contact allergens, such as para‐phenylenediamine.     

FcRγ promotes contact hypersensitivity to oxazolone without affecting the contact sensitisation process in B6 mice

The process of sensitisation by specific contact allergens is indispensable for the induction of allergic contact dermatitis. Oxazolone is a well‐characterised contact allergen. Previous studies suggested that immune cells bearing the FcRγ subunit are essential for oxazolone‐induced contact hypersensitivity, but the biological functions of the FcRγ subunit in the process of sensitisation to oxazolone remain unknown. In this study, we show that FcRγ deficiency decreases ear‐swelling responses to oxazolone in mice. However, we found that oxazolone‐sensitised FcRγ^?/? mice and oxazolone‐sensitised wild‐type (WT) mice have comparable numbers of CD11c⁺MHCII^hi dendritic cells (DCs) in their draining lymph nodes (LNs). In addition, oxazolone‐sensitised LN cells from both FcRγ^?/? and WT mice showed considerable production of interferon‐gamma (IFNγ), interleukin‐4 (IL‐4) and IL‐17A upon oxazolone‐keyhole limpet haemocyanin loading. Consistent with these data, oxazolone‐sensitised FcRγ^?/? and FcRγ^+/+ LN cells conferred contact hypersensitivity to WT naïve mice challenged with the hapten. Our findings clearly indicate that, in an experimental mouse model, the FcRγ subunit positively regulates contact hypersensitivity to oxazolone without affecting the contact sensitisation process.     

Vaccination with photodynamic therapy-treated macrophages induces highly suppressive T-regulatory cells

Background/purpose: The present study explores whether photodynamic therapy (PDT)‐induced apoptosis can increase the number of tolerogenic regulatory T cells (Treg) and limit collateral tissue damage. Methods: BALB/c mice were vaccinated subcutaneously three times with PDT‐induced apoptotic or thaw‐frozen, necrotic non‐infected autologous macrophages (MΦ). Two weeks after the last vaccination, mice were infected intradermally with 10⁶ promastigotes of Leishmania major. Results: Mice that received PDT‐induced apoptotic MΦ had fewer parasites and higher numbers of Treg than mice vaccinated with thaw‐frozen necrotic MΦ or phosphate‐buffered saline (PBS). Interleukin (IL)‐4 and IL‐6 were significantly suppressed, while IL‐10 was increased in mice that received the PDT‐induced apoptotic MΦ. The role of Treg in this process was confirmed through Treg transfer from vaccinated to naïve mice. Mice receiving CD4⁺CD25⁺ cells from mice vaccinated with PDT‐induced apoptotic MΦ showed smaller lesions 3 weeks after infection and lower parasitic burdens than mice that received Tregs from mice of thaw‐frozen necrotic MΦ or PBS groups. These changes were mediated by the depletion of CD3⁺CD8⁺ and NKT cells and increased levels of IL‐12p70 and interferon‐γ, IL‐10, and TGF‐β in the cutaneous leishmaniasis lesions. Conclusion: Vaccination with apoptotic MΦ‐induced tolerogenic Treg cells that limited collateral tissue damage and diminished parasitic burden.     

Skin application of ketoprofen systemically suppresses contact hypersensitivity by inducing CD4+ CD25+ regulatory T cells

BackgroundKetoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug that inhibits prostaglandin biosynthesis. We have previously shown that topical KP treatment at the sensitizing site inhibits the development of contact hypersensitivity (CHS) to picryl chloride (PCl).ObjectiveWe investigated the mechanism underlying the KP-induced immunosuppression of CHS by application of KP.MethodsWe analyzed the CHS responses to the non-sensitizing site and subsequent sensitization with PCl, and by transfer of the draining lymph node cells (LNCs) from KP-tolerated mice to recipient mice. Changes in the Foxp3 expression of LNCs from KP-phototreated skin were also examined by real-time PCR.ResultsTopical application of KP to not only the sensitizing but also non-sensitizing site suppressed CHS response. The immunosuppression was transferred with LNCs from mice treated with PCl plus KP, but not from mice treated oxazolone plus KP. In this transfer study, the CD4⁺ CD25⁺ subset of LNCs exerted the suppressive effect, while CD25⁺ cell-depleted LNCs lost the inhibitory ability. CTLA-4 blocking with a specific antibody, but not IL-10 blocking, abrogated the activity of CD4⁺ CD25⁺ cells. Moreover, Foxp3 mRNA expression was remarkably increased in LNCs from PCl and KP-treated mice.ConclusionThe immunosuppression of CHS by topical application of KP is systemic and haptein-specific. Treg cells play an important role in the suppressive effect by KP.     

Contact sensitization induces proliferation of heterogeneous populations of hapten-specific T cells1

Abstract To characterize the T cells that are activated during the induction of contact hypersensitivity (CH), two sets of studies were conducted: 1) dinitrophenol (DNP)-specific proliferative responses of T cells in draining lymph nodes of BALB/c mice sensitized epicutaneously to dinitro-fluorobenzene (DNFB) were examined, and 2) from these lymph node cells, DNP-specific T cells were cloned by limiting dilution microculture and analyzed by FACS for surface markers, by RT-PCR, HT2 bioassay and ELISA for cytokine expression at mRNA and protein levels respectively, and by proliferation assay for cytokine and antigen-presenting cell (APC) requirements. Our results show that αβ TCR-bearing T cells of both the CD4⁺ and CD8⁺ subtypes from lymph nodes of DNFB-skin-painted mice proliferate specifically to dinitrobenzene sulfonate (DNBS) in vitro. Four DNP-specific, CD4⁺ T-cell clones were characterized: clone 5S4 secreted IL-4 and required 11-4 for optimal growth; clone 5S10 secreted IL-2 and required 1L-2 for optimal growth; clone 5S2 secreted IL-4 but required IL-2 for optimal growth; and clone 5S8 secreted IL-2 predominantly at 5 months, but switched to production of IL-4 at 7 months. All four clones secreted IL-10, and proliferated to DNBS when Langerhans cell (LC)-enriched epidermal cells were used as APC. These findings indicate that heterogeneous populations of DNP-specific T cells are activated in draining lymph nodes during the induction of CH to DNFB in BALB/c mice.     

Impaired T‐cell‐dependent protection against Leishmania major infection in HIV‐positive patients is associated with worsened disease outcome

Cutaneous leishmaniasis (CL) patients coinfected with HIV are known to show a more severe, prolonged course of disease; the immunological basis is not known. We now assessed clinical features, sera and skin biopsies of HIV⁺ and HIV^? patients with CL to identify drivers of increased susceptibility to Leishmania. CL lesion numbers, surface, and healing duration were significantly increased in HIV⁺ as compared to HIV^? patients (2.5, 14 and >4‐fold, respectively). Patients with HIV infection exhibited lower serum Leishmania‐specific IgG levels and decreased IL‐6 and IL‐8. Most importantly, dramatically decreased numbers of CD4⁺ T cells (approximately eightfold), but not CD8⁺ cells, together with fewer CXCR3⁺ Th1 cells, fewer Foxp3⁺ effector/regulatory T cells, and reduced levels of IFN‐γ expression were found in lesional skin. Our findings suggest that compromised CD4⁺ T‐cell responses may be responsible for worsened disease outcome leading to defects in parasite elimination in the absence of sufficient numbers of IFN‐γ‐producing Th1 cells.     

Induction of regulatory T cells by leflunomide in a murine model of contact allergen sensitivity

Allergic contact dermatitis and contact hypersensitivity (CHS) are characterized by allergen-specific activation of CD8+ and CD4+ T cells and the production of cytokines resulting in an inflammatory response and tissue damage. We show here that the immunosuppressive compound leflunomide (N-[4-trifluoro-methylphenyl]-5-methylisoxazol-4 carboxamide, HWA 486) (LF) inhibited the contact allergic response induced in mice by epicutaneous application of the haptens dinitrofluorobenzene (DNFB) and oxazolone. The extent of ear swelling remained significantly reduced following repeated challenge with DNFB for up to 18 weeks. LF and DNFB had to be applied simultaneously for inhibition to occur. The loss of CHS responses was shown to be antigen-specific. Adoptive transfer of leukocytes from LF-treated mice into na?ve mice resulted in a loss of CHS responsiveness. Transfer of both CD4+ and CD8+ cells was required for maximal loss of CHS responses, with CD8+ cells playing a major role. Significantly enhanced levels of IL-10 mRNA were detected in CD8+ T cells, but not in CD4+ T cells, following LF treatment of mice. LF also suppressed CHS responses in mice previously sensitized and challenged with hapten, when administered together with the hapten. Our data suggest that LF induces a long-lived tolerance in mice by inducing CD8+ and CD4+ regulatory T cells.     

Cannabinoid 1 receptors in keratinocytes attenuate fluorescein isothiocyanate‐induced mouse atopic‐like dermatitis

Atopic dermatitis is a chronic inflammatory disease characterized by an impaired epidermal barrier function combined with a chronic Th2‐type inflammatory response and an intense pruritus. Here, we used an experimental mouse model for Th2‐type contact hypersensitivity (CHS) to fluorescein isothiocyanate (FITC) to investigate the potential role of cannabinoid 1 receptors (CB1) in the pathophysiology of mouse atopic‐like dermatitis. Mice lacking CB1 receptors globally (Cnr1^?/?) or specifically in keratinocytes (KC‐Cnr1^?/?) as well as wild‐type (WT) control mice were sensitized and challenged with FITC. We examined ear swelling responses, transepidermal water loss, Th2‐type skin inflammatory responses and serum IgE levels. Both Cnr1^?/? and KC‐Cnr1^?/? showed enhanced CHS responses to FITC and a delayed epidermal barrier repair when compared with WT mice. mRNA levels for IL‐4, thymic stromal lymphopoietin (TSLP) and CCL8, as well as eosinophil activity, were significantly increased in inflamed ear tissue of FITC‐challenged Cnr1^?/? and KC‐Cnr1^?/? mice. Importantly, CB1 receptor‐deficient keratinocytes secreted increased levels of TSLP, a proinflammatory mediator that drives Th2‐type skin inflammation in atopic dermatitis, under basal and Th2‐type inflammatory conditions. Taken together, our results demonstrate that CB1 receptors in keratinocytes help to maintain epidermal barrier homoeostasis and attenuate Th2‐type allergic inflammatory responses. Based on our work, we propose that enhanced epidermal allergen penetrance cooperates with increased production of TSLP and CCL8 by epidermal keratinocytes for the induction of type 2 CD4+ T helper cells. Our results place keratinocytes at the cross‐roads of outside‐in and inside‐out pathophysiologic mechanisms of atopic dermatitis.     

Deficient contact hypersensitivity reaction in CD4-/- mice is because of impaired hapten-specific CD8+ T cell functions

Mice deficient in the CD4 molecule (CD4-/-) are widely used to evaluate the requirement for CD4+ T cell help in viral, tumoral, and transplantation immunity. Previous studies, showing that CD4-/- mice develop impaired contact hypersensitivity (CHS) responses, have suggested that CD4+ T cells are required for the optimal induction of this skin inflammatory reaction. other studies have, however, demonstrated that CHS was mediated by CD8+ T cells, without the need for CD4+ T cell help. Here, we show that CD4-/- mice develop a normal delayed-type hypersensitivity response to protein antigen, which is mediated by major histocompatibility molecules class II-restricted CD4-CD8- T cells, but a decreased CHS response to 2,4-dinitro-fluorobenezene. Analysis of the hapten-specific T cell pool demonstrates that priming of CD8+ T cells occurred normally in CD4-/- mice, as assessed by specific proliferative responses and interferon-gamma (IFN-gamma) production of purified CD8+ T cells. Furthermore, CD8+ T cells were able to adoptively transfer a normal CHS reaction. In contrast, total lymph node cells from CD4-/- mice showed decreased IFN-gamma production and diminished specific cytotoxic T lymphocytes (CTL) activity, which could be reversed by in vitro restimulation with hapten-pulsed class II-deficient antigen-presenting cells. These data confirm that class I-restricted CD8+ T cells can fully develop in effectors of CHS in the absence of CD4+ T cell help and suggest that the impaired CHS in CD4-/- mice is because of the presence of a class II-restricted T cell subset, which controls CHS by inhibiting hapten-specific CTL responses.     

CD8+ lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury

The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage‐associated molecular patterns (DAMPs), as opposed to pathogen‐associated molecules (PAMPs), regulate the immune response to non–self‐antigens presented at the site of a physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterized by local cell death and caspase‐1 activation without demonstrably disrupting skin integrity. Co‐delivery of ovalbumin (OVA) with heat injury induces OVA‐specific CD8⁺ T‐cell responses, and this is dependent on caspase‐1 activation and MyD88 signalling. Using Id2flox/flox‐CD11cCre+ mice, we demonstrate that CD8⁺ lineage DCs are required to induce OVA‐specific CD8⁺ T‐cell responses following heat injury. Consistent with this observation, intradermal administration of CD8⁺ lineage DCs but not CD11b⁺ lineage DCs restores priming of CD8⁺ T‐cell responses in Casp‐1^?/? mice. Thus, we conclude that a sterile injury induces CD8⁺ T‐cell immune responses to local antigen through caspase‐1 activation and requires CD8⁺ lineage DCs, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity.     

Effective induction of melanoma‐antigen‐specific CD8+ T cells via Vγ9γδT cell expansion by CD56high+ Interferon‐α‐induced dendritic cells

Dendritic cells (DCs) can be differentiated from CD14⁺ monocytes in the presence of interferon‐α (IFNα) and granulocyte/macrophage‐colony stimulating factor (GM‐CSF) in vitro and are known as IFN‐DCs. Circulating blood CD56⁺ cells expressing high levels of CD14, HLA‐DR and CD86 have been shown to spontaneously differentiate into DC‐like cells in vitro after their isolation from blood. We show here that IFN‐DCs expressing high levels of CD56 (hereafter, CD56^high+ IFN‐DCs) can be differentiated in vitro from monocytes obtained as adherent cells from healthy donors and patients with metastatic melanoma. These cells expressed high levels of CD14, HLA‐DR and CD86 and possessed many pseudopodia. These CD56^high+ IFN‐DCs may be an in vitro counterpart of the circulating CD56⁺ CD14⁺ CD86⁺ HLA‐DR⁺ cells in blood. Conventional mature DCs differentiated from monocytes as adherent cells in the presence of GM‐CSF, IL‐4 and TNF‐α (hereafter, mIL‐4DCs) did not express CD56 or CD14. In contrast to mIL‐4DCs, the CD56^high+ IFN‐DCs exhibited a stronger capacity to stimulate autologous CD56⁺ Vγ9γδT cells highly producing IFNγ in the presence of zoledronate and IL‐2. The CD56^high+ IFN‐DCs possessing HLA‐A*0201 effectively induced Mart‐1‐modified melanoma peptide (A27L)‐specific CD8⁺ T cells through preferential expansion of CD56⁺ Vγ9γδT cells in the presence of A27L, zoledronate and IL‐2. Vaccination with CD56^high+ IFN‐DCs copulsed with tumor antigens and zoledronate may orchestrate the induction of various CD56⁺ immune cells possessing high effector functions, resulting in strong immunological responses against tumor cells. This study may be relevant to the design of future clinical trials of CD56^high+ IFN‐DCs‐based immunotherapies for patients with melanoma.     

Propionibacterium acnes vaccination induces regulatory T cells and Th1 immune responses and improves mouse atopic dermatitis

Abstract: Atopic dermatitis (AD) is a chronic disease characterized by a polarized Th2 immune response. Propionibacterium acnes (P. acnes) has been shown to elicit strong Th1 immune responses. We hypothesized that the host immune response to P. acnes will prevent the development of AD. To demonstrate this hypothesis, we investigated the effect of P. acnes vaccination on AD that occurs in keratin 14/driven caspase‐1 transgenic mouse. Vaccination with low dose of P. acnes successfully prevented clinical manifestations in the skin of AD mice associated with systemic and cutaneous increased expression of Th1‐type cytokines but without suppression of Th2 cytokines. Interestingly, the numbers of IFN‐γ⁺T cells, FoxP3⁺CD4⁺CD25⁺T cells (nTreg) and IL‐10⁺T cells (Tr1) were significantly increased in the spleen. P. acnes vaccination has effects to alter the cytokine milieu and may be useful for the improvement of atopic symptom.     

Narrowband ultraviolet B radiation suppresses contact hypersensitivity

Background/purpose: A main mechanism responsible for the efficacy of narrowband ultraviolet (UV)B is thought to be the induction of apoptosis in pathogenetically relevant cells. Narrowband UVB therapy, however, generally induces a relatively long remission period. Recently, evidence that UVB radiation induces regulatory T (Treg) cells was reported. Based on these findings, we examined whether narrowband UVB suppresses contact hypersensitivity (CHS) by inducing Treg cells. Methods: The shaved abdomens of C3H/HeN mice were irradiated with broadband or narrowband UVB. CHS was defined as an ear‐swelling response. To examine whether tolerance can be induced by adoptive transfer, lymph node cells from UVB‐irradiated mice were injected into naïve mice before sensitization and CHS challenge. Results: Narrowband UVB exposure dose dependently suppressed CHS. Significant suppression was observed at doses between 1000 and 3000 mJ/cm² (P<0.05). The suppressive effect achieved with 1000 mJ/cm² narrowband UVB was very similar to the effect achieved with 100 mJ/cm² broadband UVB. The suppressive effects on CHS were transferred to naïve mice by the injection of lymph node cells from tolerant mice. Conclusion: Narrowband UVB induced local and systemic suppression of CHS. In addition, narrowband UVB induces tolerance to CHS and the suppressive effects were transferable to naïve mice.