Systemic Suppression Of Contact Hypersensitivity Research Articles

Narrowband ultraviolet B radiation suppresses contact hypersensitivity

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. 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. Narrowband UVB exposure dose dependently suppressed CHS. Significant suppression was observed at doses between 1000 and 3000 mJ/cm(2) (P<0.05). The suppressive effect achieved with 1000 mJ/cm(2) narrowband UVB was very similar to the effect achieved with 100 mJ/cm(2) broadband UVB. The suppressive effects on CHS were transferred to naïve mice by the injection of lymph node cells from tolerant mice. 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.

Radiation Sources Providing Increased UVNUVB Ratios Induce Photoprotection Dependent on the UVA Dose in Hairless Mice

In studies involving mice in which doses of UVA (320-400 nm) and UVB (290-320 nm) radiation were administered alone or combined sequentially, we observed a protective effect of UVA against UVB-induced erythema/edema and systemic suppression of contact hypersensitivity. The UVA immunoprotection was mediated by the induction of the stress enzyme heme oxygenase-1 (HO-1) in the skin, protection of the cutaneous Th1 cytokines interferon-gamma (IFN-gamma) and IL-12 and inhibition of the UVB-induced expression of the Th2 cytokine IL-10. In this study, we seek evidence for an immunological waveband interaction when UVA and UVB are administered concurrently to hairless mice as occurs during sunlight exposure in humans. A series of spectra providing varying ratios of UVA/UVB were developed, with the UVA ratio increased to approximately 3.5 times the UVA component in solar simulated UV (SSUV). We report that progressively increasing the UVA component of the radiation while maintaining a constant UVB dose resulted in a reduction of both the erythema/edema reaction and the degree of systemic immunosuppression, as measured as contact hypersensitivity. The UVA-enhanced immunoprotection was abrogated in mice treated with a specific HO enzyme inhibitor. UVA-enhanced radiation also upregulated the expression of cutaneous IFN-gamma and IL-12 and inhibited expression of both IL-6 and IL-10, compared with the activity of SSUV. The results were consistent with the previously characterized mechanisms of photoprotection by the UVA waveband alone and suggest that the UVA component of solar UV may have beneficial properties for humans.

20 years after--milestones in molecular photobiology.

Ultraviolet radiation represents one of the most relevant environmental factors because of its hazardous health effects, which include induction of skin cancer, premature skin aging, and exacerbation of infectious diseases. The biologic effects exerted by ultraviolet radiation have been well characterized by a variety of in vitro and in vivo studies. The events taking place inside the cell during the ultraviolet response, however, remained unclear for quite a long time. Molecular photobiology has increased our knowledge about ultraviolet-induced signal transduction enormously within the last 10 years. For a long time, nuclear DNA has been regarded as the only chromophore for ultraviolet radiation. Today we know that ultraviolet radiation can affect also other molecular targets located in the cytoplasm and at the cell membrane. These targets include cell surface receptors, kinases, phosphatases, and transcription factors. Detailed knowledge about ultraviolet-induced signal transduction will certainly increase our understanding of how ultraviolet radiation exerts its biologic effects and furthermore will provide us with tools to interfere with these pathways, thereby reducing the adverse effects of ultraviolet radiation.

Ultraviolet A Irradiation of C57BL/6 Mice Suppresses Systemic Contact Hypersensitivity or Enhances Secondary Immunity Depending on Dose

Ultraviolet radiation is the most common environmental carcinogen humans are exposed to. It is now known that in order for skin cancers to develop, both genetic damage and immunosuppression is required. Ultraviolet-induced immunosuppression is therefore a key contributor to the development of skin cancer. Little is known about the relative contributions of the different ultraviolet spectra (A and B), however. Therefore detailed ultraviolet dose-response curves for systemic suppression of contact hypersensitivity in two mouse strains were determined to examine the relative contributions of each of these spectral components of sunlight to primary and secondary immunity. Whereas ultraviolet B caused a linear dose-related immunosuppression in both C57BL/6 and Balb/c mice, only C57BL/6 mice were immunosuppressed by medium doses of ultraviolet A. At higher ultraviolet A doses, C57BL/6 mice were protected from immunosuppression, suggesting a genetic predisposition to ultraviolet-A-induced immunomodulation. Surprisingly, we found that, in contrast to primary immunosuppression, low dose ultraviolet A enhanced the secondary immune response, whereas ultraviolet B caused antigen-specific tolerance. When ultraviolet A and ultraviolet B were combined to mimic sunlight (solar-simulated ultraviolet), immunosuppression and tolerance were only observed over a narrow dose range as the memory-enhancing effect of low dose ultraviolet A and the immunoprotective effect of higher dose ultraviolet A prevented the suppressive effects of ultraviolet B. These studies suggest that complex relationships between ultraviolet dose, immunomodulation, spectra, and genetic background are likely to be important for skin cancer induction. We also describe for the first time that low doses of ultraviolet A are able to enhance secondary immunity, which has important implications for vaccination strategies.

Improved Protection Against Solar-Simulated Radiation-Induced Immunosuppression by a Sunscreen with Enhanced Ultraviolet A Protection

Ultraviolet radiation-induced immunosuppression is thought to play a part in skin cancer. Several studies have indicated that sunscreens that are designed to protect against erythema failed to give comparable protection against ultraviolet radiation-induced immunosuppression. One possible reason for this discrepancy is inadequate ultraviolet A protection. This study evaluated the level of immunoprotection in mice afforded by two broad-spectrum sunscreens with the same sun protection factor, but with different ultraviolet A protection factors. Both sunscreens contained the same ultraviolet B and ultraviolet A filters, in the same vehicle, but at different concentrations. Solar simulated radiation dose-response curves for erythema, edema, and systemic suppression of contact hypersensitivity were generated and used to derive protection factors for each end-point. The results of three different techniques for determining immune protection factor were compared. A comparison of the two sunscreens showed that the protection factor for erythema in mice was similar to that determined in humans (sun protection factor) but the protection factor for edema in mice was lower. Both sunscreens protected against suppression of contact hypersensitivity but the product with the higher ultraviolet A-protection factor showed significantly greater protection. The three techniques for determining immunoprotection gave very similar results for a given sunscreen, but immune protection factor was always lower than sun protection factor. These data suggest that sun protection factor may not predict the ability of sunscreens to protect the immune system and that a measure of ultraviolet A protection may also be necessary.

Photoprotection: sunscreens and the immunomodulatory effects of UV irradiation

UV-B irradiation (UVR) of the host, in both humans and animal models, induces dose-related acute and chronic changes in skin which include erythema and photoageing, and induction of cancer. It can also induce modulation of immune responses of the host to antigens presented following irradiation. Commercially-available, broad-spectrum, high SPF (15, 15+) sunscreens protect against most effects of UV irradiation. An exception is the effects of UVR on immune responsiveness, with varying degrees of protection having been reported. We examined a system of UV-induced systemic suppression of contact hypersensitivity (CHS) responses in BALB/c mice. A range of commercially-available, broad spectrum, high SPF (15+) sunscreens demonstrated at best partial protection against systemic immunosuppression, yet were able to protect against two hallmarks of acute UVR-induced damage: skin oedema and keratinocyte proliferation. Two major models have been identified for the induction of immunosuppression following UVR, one identifying trans-urocanic acid ( trans-UCA; deaminated histidine, located in the stratum corneum) as the critical photoreceptor, the other featuring DNA. UVR of trans-UCA produces cis-UCA, which itself is immunomodulatory. There was some abrogation of trans to cis isomerisation of urocanic acid in UV-irradiated, sunscreen-protected mice. However, the majority of the immunomodulation seen in these mice was abrogated by pretreatment with a monoclonal antibody to cis-urocanic acid. It is possible to induce formation of cis-urocanic acid in BALB/c skin in the absence of immunosuppression, using lower doses of UV radiation, indicating that formation of cis-urocanic acid in the stratum corneum is not necessarily sufficient to induce immunosuppression in the UV-irradiated host. The mechanisms of induction of the immunomodulated state in the UV-irradiated host are potentially diverse and the subject of ongoing debate. Our studies maintain a role for cis-UCA, and form the basis for further studies on its involvement in immunomodulation by UVR in sunscreen-protected hosts.

Glutathione Ethylester Protects against Local and Systemic Suppression of Contact Hypersensitivity Induced by Ultraviolet B Radiation in Mice

Irradiation of the skin with ultraviolet B (UVB) radiation causes a local and systemic suppression of T-cell-mediated immune responses. Recently, N-acetylcysteine was found to protect against UVB-radiation-induced immunosuppression and several other types of damage induced by UV radiation. The protective effects appeared to be caused by an increase in glutathione (GSH). This increase was limited by feedback inhibition by GSH of its own synthesis. Better results were expected with the use of GSH derivatives which do not require de novo synthesis, such as GSH esters. In this study, topical application of glutathione ethylester (GSH-Et) was found to increase the epidermal GSH level in mice in a manner that was dependent on dose to 1234% of the control value at the highest dose tested (2.0 micromol/cm2). This resulted in dose-dependent protection against UVB-radiation-induced suppression of contact hypersensitivity. The highest dose of GSH-Et tested provided 83% protection against local suppression and 62% protection against systemic suppression. Immunosuppression induced by topically applied cis-urocanic acid (cis-UCA) was prevented completely. Although an effect on the formation of pyrimidine dimers cannot be excluded, the protective effect of GSH-Et seems to be mediated through inhibition of the action of cis-UCA.

Urocanic Acid Does not Photobind to DNA in Mice Irradiated with Immunosuppressive Doses of UVB*

ABSTRACTUltraviolet B (UVB, 290–320 nm) radiation initiates in vivo a dose‐ and wavelength‐dependent down regulation of cell‐mediated immunity. An action spectrum for UV‐induced immunosuppression indicated that the photoreceptor for this effect is urocanic acid (UCA), which undergoes a trans to cis isomerization in the stratum corneum on UV exposure. An accumulation of evidence has supported this conclusion. However, evidence has a/so been presented that formation of thymine dimers in DNA is responsible for initiation of UV‐induced immunosuppression. Because photobinding of UCA to DNA in vitro forming cyclobutane‐type adducts has been shown, we sought to resolve this dilemma by investigating if UCA photobinds to DNA in vivo. The [14C]cis‐UCA, [14C]trans‐UCA or [3H]8‐MOP (8‐methoxypsoralen) was applied topically to BALB/c mice that were then irradiated with a dose of UV previously shown to cause systemic suppression of contact hypersensitivity. The DNA was prepared from epidermal cells by phenol extraction immediately after in vivo irradiation and bound radioactivity determined. Although photobinding of [3H]8‐MOP was readily demonstrable under these conditions (0.9 nmol/mg DNA), no significant binding of either isomer of UCA to DNA (between 1.2 × 10−3 and 2.1 × 10−3 ng/mg DNA) could be detected. Uptake studies in keratinocytes prepared from epidermis of untreated animals indicated that [3H]8‐MOP was taken up with a rate constant of 4.2 × 10−3 pmol/s/mg protein/μmol/L. In contrast, uptake of [14C]cis‐UCA was not statistically significant from zero and uptake of [14C]trans‐UCA was negligible (0.8 × 10−3± 0.08 × 10 3 pmol/s/mg protein/μmol/L). There was no significant difference between uptake of UCA isomers but uptake of [3H]8‐MOP was significantly greater than that of either UCA isomer (P &lt; 0.01). These studies indicate that the photobinding of UCA to DNA does not play a role in UV‐induced immunosuppression.

Urocanic acid does not photobind to DNA in mice irradiated with immunosuppressive doses of UVB.

Ultraviolet B (UVB, 290-320 nm) radiation initiates in vivo a dose- and wavelength-dependent down regulation of cell-mediated immunity. An action spectrum for UV-induced immunosuppression indicated that the photoreceptor for this effect is urocanic acid (UCA), which undergoes a trans to cis isomerization in the stratum corneum on UV exposure. An accumulation of evidence has supported this conclusion. However, evidence has also been presented that formation of thymine dimers in DNA is responsible for initiation of UV-induced immunosuppression. Because photobinding of UCA to DNA in vitro forming cyclobutane-type adducts has been shown, we sought to resolve this dilemma by investigating if UCA photobinds to DNA in vivo. The [14C]cis-UCA, [14C]trans-UCA or [3H]8-MOP (8-methoxypsoralen) was applied topically to BALB/c mice that were then irradiated with a dose of UV previously shown to cause systemic suppression of contact hypersensitivity. The DNA was prepared from epidermal cells by phenol extraction immediately after in vivo irradiation and bound radioactivity determined. Although photobinding of [3H]8-MOP was readily demonstrable under these conditions (0.9 nmol/mg DNA), no significant binding of either isomer of UCA to DNA (between 1.2 x 10(-3) and 2.1 x 10(-3) ng/mg DNA) could be detected. Uptake studies in keratinocytes prepared from epidermis of untreated animals indicated that [3H]8-MOP was taken up with a rate constant of 4.2 x 10(-3) pmol/s/mg protein/mumol/L. In contrast, uptake of [14C]cis-UCA was not statistically significant from zero and uptake of [14C]trans-UCA was negligible (0.8 x 10(-3) +/- 0.08 x 10(-3) pmol/s/mg protein/mumol/L). There was no significant difference between uptake of UCA isomers, but uptake of [3H]8-MOP was significantly greater than that of either UCA isomer (P < 0.01). These studies indicate that the photobinding of UCA to DNA does not play a role in UV-induced immunosuppression.

Sunscreens Offer the Same UVB Protection Factors for Inflammation and Immunosuppression in the Mouse

Many studies report that sunscreens effective against UVR-induced inflammation afford poor protection against immunosuppression. We have studied the relationship between photoprotection of inflammation and immunosuppression with monochromatic UVB (Philips TL01 tubes, lambda max = 311 nm) to remove possible confounding effects of differences in end point action spectra. Dose-response curves for edema and systemic suppression of contact hypersensitivity (CHS) in HRA.HRII-c/+/Skh mice showed that suppression of CHS was more sensitive to UVB irradiation by a factor of 2. The UVB dose-response curve for murine edema was similar to that for human erythema, with threshold doses of 773 mJ x cm(-2) and 632 mJ x cm(-2), respectively. The protection afforded by two UVB filters, octyl dimethyl para-aminobenzoic acid and 2-ethylhexyl-4'-methoxycinnamate, prepared in an identical vehicle, each with the same optical density at 311 nm, was tested in mice. We applied sunscreen to all exposed skin or to transpore tape above the irradiation cages, prior to exposure with 2.8 minimal edema doses. Topical or tape application of both sunscreens protected totally against edema but only partially against immunosuppression, with no significant difference in protection between the two application techniques (p > 0.4). A sunscreen protection factor of 4 in vivo was determined for 2-ethylhexyl-4'-methoxycinnamate for both edema and immunosuppression. Failure of the sunscreens to protect completely against immunosuppression was due to the ability of subedemal doses of UVB to induce substantial immunosuppression and not, as previously suggested, to any skin interaction.

Differential effects of a monoclonal antibody to cis-urocanic acid on the suppression of delayed and contact hypersensitivity following ultraviolet irradiation.

Urocanic acid (UCA) occurs naturally in the stratum corneum of the skin as the trans-isomer and, upon exposure to UVB radiation, converts to cis-UCA. It has been proposed that trans-UCA is the photoreceptor for and, following its isomerization to cis-UCA, a mediator of the suppressive effects of UVB irradiation on systemic T cell-mediated immune responses, such as contact hypersensitivity (CH) and delayed-type hypersensitivity (DTH). To address this question directly, we studied the consequence of deleting the in vivo function of cis-UCA on systemic suppression of CH and DTH, by injecting mice with a anti-cis-UCA mAb several hours before exposure to UVB radiation. We found that while DTH responses were completely restored, the anti-cis-UCA Ab had no effect on UV-induced immunosuppression of the CH response, even though suppressor cell formation was inhibited in both cases. Further, the kinetics of IL-10 expression in the skin of irradiated mice injected with the anti-cis-UCA mAb was altered and the diminished APC function of spleen-adherent cells from UVB-irradiated mice was totally reversed by the Ab. These findings suggest that cis-UCA acts as a mediator for some but not all of the systemic suppressive effects of UVB irradiation. They also suggest that cis-UCA may act indirectly via IL-10 to modulate immune function.

Dietary Butter Protects against Ultraviolet Radiation-Induced Suppression of Contact Hypersensitivity in Skh:HR-1 Hairless Mice

Dietary fats modulate a wide variety of T cell functions in mice and humans. This study examined the effects of four different dietary fats, predominantly polyunsaturated sunflower oil, margarine, and predominantly saturated butter, clarified butter, on the T cell-mediated, systemic suppression of contact hypersensitivity by ultraviolet radiation in the Skh:HR-1 hairless mouse. Diets containing either 200 g/kg or 50 g/kg butter or clarified butter as the sole fat source protected against systemic photoimmunosuppression, whether the radiation source was unfiltered ultraviolet B (280–320 nm) or filtered solar simulated ultraviolet radiation (290– 400 nm), in comparison with diets containing either 200 or 50 g/kg margarine or sunflower oil. There was a linear relationship (r > 0.9) between protection against photo-immunosuppression and the proportion of clarified butter in mice fed a series of 200 g/kg mixed fat diets that provided varying proportions of clarified butter and sunflower oil. The dietary fats did not modulate the contact hypersensitivity reaction in unirradiated animals. The observed phenomena were not primarily due to the carotene, tocopherol, cholecalciferol, retinol, lipid hydroperoxide or the nonfat solid content of the dietary fats used and appeared to be a result of the different fatty acid composition of the fats.

Analysis of the Protective Effect of Different Sunscreens on Ultraviolet Radiation-Induced Local and Systemic Suppression of Contact Hypersensitivity and Inflammatory Responses in Mice

Analysis of the Protective Effect of Different Sunscreens on Ultraviolet Radiation-Induced Local and Systemic Suppression of Contact Hypersensitivity and Inflammatory Responses in Mice

Analysis of the Protective Effect of Different Sunscreens on Ultraviolet Radiation-Induced Local and Systemic Suppression of Contact Hypersensitivity and Inflammatory Responses in Mice

Analysis of the Protective Effect of Different Sunscreens on Ultraviolet Radiation-Induced Local and Systemic Suppression of Contact Hypersensitivity and Inflammatory Responses in Mice

Analysis of the Protective Effect of Different Sunscreens on Ultraviolet Radiation-Induced Local and Systemic Suppression of Contact Hypersensitivity and Inflammatory Responses in Mice

We investigated the capacity of three sunscreen compounds to protect mice from the inflammatory and immunosuppressive effects of ultraviolet radiation (UVR). The sunscreen preparations contained 7.5% 2-ethylhexyl-p-methoxycinnamate, 8% octyl-N-dimethyl-p-aminobenzoate, or 6% benzophenone-3 in an oil-in-water emulsion. Skin swelling was used as the measure of their effect on UVR-induced inflammation, and immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UV-irradiated skin (local suppression) or a distant site (systemic suppression). The sunscreens were applied to the shaved dorsal skin of C3H mice, which were then given a single dose of UVR ranging from 2 to 32 kJ/m2 within the UVB (280-320 nm) region. All three sunscreens gave complete protection against local suppression of contact hypersensitivity caused by a dose of 2 kJ/m2 UVB. They also protected against both inflammation and systemic immunosuppression caused by UVR; however, protection was highly dependent on the UVR dose. Furthermore, the sunscreens were less effective in protecting against systemic immunosuppression than against inflammation. These results indicate that immunosuppression is less sensitive to the protective effects of the sunscreens than inflammation and that protection against UVR-induced inflammation does not necessarily imply prevention of immunologic alterations. In addition, these studies suggest that UVR-induced immunosuppression and inflammation may involve different mechanisms.

Differential Protection by Two Sunscreens from UV Radiation–Induced Immunosuppression

A controversy has arisen concerning the ability of sunscreens to protect mice from the immunosuppressive effects of UV radiation. We have assessed the photoprotection in hairless mice of two sun protection factor (SPF)15 sunscreens containing different UVB (280-320-nm) absorbers, namely, octyl-N-dimethyl-p-aminobenzoate (o-PABA) or 2-ethylhexyl-p-methoxycinnamate (2-EHMC). Following three minimum erythemal exposures to UV radiation, both systemic suppression of contact hypersensitivity to 2,4-dinitrofluorobenzene and induction of susceptibility to transplanted UV radiation-induced tumor cells was established. Topically applied 2-EHMC sunscreen protected totally from both forms of immunosuppression, but the o-PABA sunscreen failed to protect, although both sunscreens were equally effective in protection from UV radiation-induced erythema and edema.

Morison WL: Systemic suppression of contact hypersensitivity associated with suppressor lymphocytes: Is a lesion in DNA an essential step in the pathway? Photodermatol Photoimmunol Photomed 7:202–206, 1990.

Morison WL: Systemic suppression of contact hypersensitivity associated with suppressor lymphocytes: Is a lesion in DNA an essential step in the pathway? Photodermatol Photoimmunol Photomed 7:202–206, 1990.

Morison WL: Systemic suppression of contact hypersensitivity associated with suppressor lymphocytes: Is a lesion in DNA an essential step in the pathway? Photodermatol Photoimmunol Photomed 7:202–206, 1990.

Morison WL: Systemic suppression of contact hypersensitivity associated with suppressor lymphocytes: Is a lesion in DNA an essential step in the pathway? Photodermatol Photoimmunol Photomed 7:202–206, 1990.

ULTRAVIOLET‐B DOSE‐RESPONSE CURVES FOR LOCAL AND SYSTEMIC IMMUNOSUPPRESSION ARE IDENTICAL

Irradiation of mice with UVB suppresses contact hypersensitivity either "locally", i.e. when sensitizer is applied to the UV irradiated site, or "systemically", i.e. when sensitizer is applied to a site distal to the site of irradiation. It has been suggested that local suppression requires lower doses of UV than does systemic suppression, and that different mechanisms are therefore responsible. We undertook a detailed analysis of the dose-response and kinetics of UV-induced local and systemic suppression of contact hypersensitivity to trinitrochlorobenzene in two strains of mice, C57BL/6 and BALB/c. We found that the UV dose-responses for systemic and local suppression were identical within the same strain. Comparison, however, of UV dose-responses between strains indicated that C57BL/6 mice required 6.4 times less UV than did BALB/c mice to generate an equivalent amount of suppression. In both strains, local suppression was initiated if sensitizer was applied immediately, or 1 or 3 days after completion of a single dose of UV. In contrast, systemic suppression was initiated only if sensitizer was applied 3 days after UV irradiation. Thus local suppression was generated in the absence of significant systemic suppression (but not vice versa), and this was dependent on time of application of sensitizer after UV irradiation, not on the dose of UV administered. Filtration of the UV source with Mylar indicated that UVB was responsible for initiating both local and systemic suppression. In summary, these results indicate that (1) genetically determined differences in susceptibility to UV suppression exist, (2) the time courses of generation of local and systemic suppression are identical, and therefore use of the terms "low dose" and "high dose" to refer respectively to local and systemic suppression by UV irradiation are incorrect. We conclude that a common mechanism initiates UV-induced local and systemic suppression of contact hypersensitivity by the immediate formation, at the site of UV irradiation, of an immunosuppressive signal which takes between 1 and 3 days to act systemically.

UVB and UVC, but Not UVA, Potently Induce the Appearance of T6-DR+ Antigen-Presenting Cells in Human Epidermis

Non-Langerhans cell, antigen-presenting T6- DR+ epidermal cells (EC) appear 3 days following broad band ultraviolet radiation exposure of human skin and are responsible for the increased antigen presentation capacity of EC seen 3 days after UV exposure. To determine the UV wavelengths that induce T6- DR+ EC, volar forearm skin of 10 human volunteers was irradiated in vivo with 4 minimal erythema doses (MED) each of pure UVA (mean 482 J cm-2), UVB (mean 0.390 J cm-2), and UVC (mean 0.397 J cm-2). The purity of the light sources was as follows: UVB, 98% of the emission was in the UVB range; UVC, 97% of the irradiance was in the UVC range; UVA, 100% of the energy had wavelengths longer than 340 nm. Three days after UV irradiation with 4 MED of each wavelength band, suction blister-derived EC suspensions were prepared from the UV-exposed and unirradiated sites. Percentages of T6+ DR+ Langerhans cells (LC) and T6- DR+ EC were quantitated. Relative to control EC, which contained 2.4 +/- 0.3% T6+ DR+ LC, the mean percentage (+/- SEM) of T6+ DR+ LC contained within UV-exposed EC was significantly decreased as follows: UVB, 0.5 +/- 0.2%; UVC, 0.9 +/- 0.1%; UVA, 0.5 +/- 0.2% (n = 10). T6- DR+ EC, absent in control EC, were induced both by UVB, 5.2 +/- 1.7% and UVC; 1.5 +/- 0.4%. Despite the use of more than 1200 times greater doses in J cm-2 of UVA than UVB and UVC, UVA was a poor inducer of T6- DR+ EC (0.5 +/- 0.2%) and in about half of these individuals, T6- DR+ EC were undetectable. The UV wavelengths for induction of T6- DR+ EC lies predominantly within the UVB band, but also to a lesser extent within the UVC band. These wavelengths appear to be analogous to both the wavelengths for generation of increased host susceptibility to UV-induced murine tumors and to the wavelengths for UV-induced systemic suppression of contact hypersensitivity. However, our data indicate that UV wavelengths for decreasing the number of T6+ DR+ LC in humans differs from the wavelengths for induction of systemic suppression of contact hypersensitivity in mice. Taken together, these data suggest that the appearance of T6- DR+ EC, but not the disappearance of T6+ DR+ LC, following UV exposure may be related to the induction of such antigen-specific suppressor T cells.