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M L Kripke

Publications and source records attributed to M L Kripke.

At least 145 records · Page 8Linked to original sources
PubMed1986

Studies on the role of antigen-presenting cells in the systemic suppression of contact hypersensitivity by UVB radiation.

Exposure of mice to UVB radiation produces a highly selective, systemic immunosuppression associated with the appearance of suppressor T lymphocytes. Suppression of delayed hypersensitivity to hapten-coupled syngeneic cells has been shown to result from an altered distribution of antigen-presenting cells. The purpose of this study was to determine whether an alteration in the activity of antigen-presenting cells could account for the systemic suppression of contact hypersensitivity (CHS) by UVB radiation. Fluorescein isothiocyanate (FITC) was used for contact sensitization because it uses different antigen-presenting cells than does oxazolone to induce CHS. Our previous studies demonstrated that CHS to oxazolone was suppressed by UVB irradiation. In these studies, we show that exposure of mice to UVB radiation before epicutaneous application of FITC onto unirradiated skin markedly decreased the CHS response to FITC painted on unexposed ears. Cyclophosphamide-sensitive suppressor T cells were detectable in the spleens of mice exhibiting decreased CHS. The antigen-presenting activity of cells in lymph nodes draining the site of epicutaneous sensitization (DLN cells) was assessed by injecting them into the hind footpads of syngeneic recipients and measuring the CHS response to FITC 6 days later. Viable DLN cells from UVB-irradiated, FITC-sensitized mice were equal to those from unirradiated, FITC-sensitized mice in their ability to induce CHS in normal recipients. No sensitization resulted when killed DLN cells were used for immunization, indicating that sensitization was not caused by reprocessing of antigen by host cells. We conclude that impairment of the CHS reaction in UVB-irradiated mice does not appear to be blocked at an initial step of antigen uptake, processing, or presentation, but must be impaired at some other step in the immunologic pathway.

Animals↗
PubMed1986

Advances in the immunobiology of the skin. Implications for cutaneous malignancies.

Recent advances in cutaneous immunobiology have led to the realization that skin is an important and unique immunologic organ. Studies on the immunobiology of skin cancers induced by ultraviolet radiation indicate that immune mechanisms can play a crucial role in the development of cutaneous tumors. This paper summarizes the evidence linking skin and the immune system and discusses current hypotheses concerning the mechanisms by which UV radiation interferes with cutaneous immunity. The significance of these findings for cutaneous carcinogenesis is discussed.

Humans↗
PubMed1986

Immunology and photocarcinogenesis. New light on an old problem.

Renewed interest in experimental photocarcinogenesis was stimulated by the observation that skin cancers induced in mice by ultraviolet radiation are highly antigenic. Most of these cancers are rejected by the immune system on transplantation into a normal, genetically identical animal. This finding raised the question of how these tumors could survive and grow progressively in the primary host without inducing immunologic rejection. Studies addressing this question produced the unexpected finding that mice that had been exposed to ultraviolet radiation, but that had not yet developed primary skin cancers, were also unable to reject transplants of these highly antigenic tumors. Thus exposing the animals to ultraviolet radiation produced a systemic alteration in the animals that interfered with the immunologic rejection of ultraviolet radiation-induced skin cancers implanted at nonirradiated sites. The failure of tumor rejection was associated with the presence of suppressor lymphocytes in the lymphoid organs of ultraviolet-irradiated mice. A question raised by the finding of suppressor lymphocytes in ultraviolet-irradiated mice is how exposure of the skin to ultraviolet radiation leads to this alteration in immune regulation. Evidence for some of the steps in this process has been accumulating for the past few years. It has been found that ultraviolet-irradiated mice have at least two other immunologic alterations; one involves the response to antigens applied topically at irradiated sites, and the other involves the response to certain antigens applied on nonirradiated skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice.

Exposing mice to UV radiation in the UVB range (280-320 nm) causes a selective immune suppression that contributes to the development of UVB-induced skin cancers. Among the immune responses suppressed by UVB irradiation are contact and delayed hypersensitivity reactions to haptens administered at unexposed sites. In these studies we provide evidence that delayed and contact hypersensitivity to the same hapten are not equivalent reactions and that they are suppressed in UVB-irradiated mice by 2 different mechanisms. This conclusion is based on the findings that: suppression of contact hypersensitivity could not be overcome by immunizing UVB-irradiated mice with hapten-coupled antigen-presenting cells derived from normal donors; and treatment of UVB-irradiated mice with methylprednisolone before immunization prevented the suppression of delayed hypersensitivity but had no effect on the suppression of contact hypersensitivity. The decreased ability to induce contact hypersensitivity in UVB-irradiated mice could be transferred to x-irradiated mice by reconstituting them with spleen cells from UVB-irradiated donors. The induction of hapten-specific suppressor cells, however, required both UVB irradiation and priming with hapten. Based on these results, we postulate that UVB irradiation induces a population of suppressor-inducer cells with specificity for a modified skin antigen and that this antigen serves as a carrier molecule for haptens that induce contact hypersensitivity and for tumor-specific transplantation antigens on UVB-induced tumors.

Animals↗
PubMed1986

Studies on the mechanism of systemic suppression of contact hypersensitivity by ultraviolet B radiation.

Exposure of mice to ultraviolet (UV) B radiation (280-320 nm) induces suppressor T lymphocytes (Ts) that prevent the rejection of primary skin cancers. A model for understanding how UVB radiation activates the suppressor cell pathway is based on the finding that UVB irradiation of mice also induces hapten-specific Ts following application of a contact sensitizing agent to unirradiated skin. Studies presented here address the mechanism by which the Ts pathway is activated in UV-irradiated mice. The hypothesis tested is that the induction of Ts results from a direct alteration of circulating antigen-presenting cells (monocytes) by the radiation. This hypothesis predicts that the UV-induced suppression of contact hypersensitivity will be reversed by replacing the antigen-presenting cells (monocytes or macrophages) after irradiation. To test this prediction, UVB-irradiated mice were given normal bone marrow cells, spleen fragments, splenic antigen-presenting cells, or stimulants of endogenous bone marrow cells. None of these procedures reversed the effects of the irradiation. Furthermore, immunization of UVB-irradiated mice with hapten-coupled splenic macrophages also failed to restore the contact hypersensitivity reaction. Therefore, direct inactivation of circulating monocytes does not appear to be the mechanism by which UVB radiation induces Ts. Experiments are also presented indicating that passive accumulation of inflammatory cells in the skin does not explain the UVB-induced systemic suppression of contact hypersensitivity. Collectively, these results support the hypothesis that a soluble mediator, induced by exposure of the skin to UVB radiation, is involved in UVB-induced systemic immunosuppression.

Animals↗
PubMed1986

Suppressor lymphocytes induced by epicutaneous sensitization of UV-irradiated mice control multiple immunological pathways.

The purpose of this study was to determine whether the formation of hapten-specific suppressor T lymphocytes induced by the epicutaneous sensitization of UV-irradiated mice could suppress other hapten-specific immune responses in addition to contact hypersensitivity (CHS). Suppressor cells were induced by applying trinitrochlorobenzene (TNCB) to the unexposed skin of mice irradiated several days earlier with 40 kJ/m2 UVB (280-320 nm) radiation. Previous work demonstrated that the spleens of such animals contain Lyt-1+, 2-T lymphocytes which prevent the induction of CHS to TNCB when transferred to normal mice, and inhibit proliferation of normal lymphocytes in vitro to TNP-modified syngeneic cells. These studies show that addition of T lymphocytes from UV-irradiated, TNCB-sensitized mice to cultures of normal lymphocytes and TNP-modified syngeneic cells inhibited the generation of TNP-specific cytotoxic T lymphocytes (CTL). The inhibition was dose-dependent and occurred only when the suppressor cells were present during the first 24 hr of culture. The suppressor cells had no effect on the activity of preformed CTL. In addition, injection of the suppressor lymphocytes into mice at the time of i.v. injection of TNP-modified sheep red blood cells (TNP-SRBC) reduced the number of direct plaque-forming cells against TNP, but had no effect on the production of antibody against SRBC. Cells that inhibited anti-TNP antibody formation were Thy-1+, Lyt-1+, 2-. These results indicate that hapten-specific suppressor cells from UV-irradiated mice prevent the activation of several different hapten-specific immunological pathways.

Animals↗
PubMed1985

Modulation of immune function by UV radiation.

In addition to its carcinogenic activity, ultraviolet (UV) radiation is capable of modifying certain immunologic reactions. Immunologic alterations induced in mice by UV radiation include both local and distant effects. Local alterations result from a direct effect of UV radiation on an immune reaction that takes place at the site of irradiation. Distant alterations are those in which exposure of skin to UV radiation at one site modifies an immune reaction occurring at a distant, unexposed site. Based on recent studies, we propose that there may be two types of distant alterations. One is nonspecific, may be due to accumulation of leukocytes at the site of UV-induced inflammation, and is exemplified by the suppression of delayed hypersensitivity and local graft-versus-host (GVH) reactions. The second may result from DNA damage, may involve a soluble mediator, and is manifested by the systemic suppression of contact hypersensitivity and the formation of antigen-specific suppressor T lymphocytes. These immunologic effects of exposure to UV radiation may be important in the pathogenesis of skin cancer and other cutaneous diseases.

Animals↗
PubMed1985

Effect of sunlight and its component wavebands on contact hypersensitivity in mice and guinea pigs.

Exposure of mice to UVB (280-320 nm) radiation is known to suppress the development of contact hypersensitivity (CHS) to chemicals that are applied subsequently to unirradiated skin, and this suppression is associated with the generation of suppressor lymphocytes. In this study, the systemic effect of other wavebands of nonionizing radiation on the development of CHS has been tested. Large doses of visible (greater than 400 nm) radiation produced a small but consistent systemic suppression of CHS in mice. In contrast, a large dose of UVA (320-400 nm) radiation did not suppress CHS but, rather, enhanced this immune response. Exposure of both mice and guinea pigs to sunlight produced systemic suppression of CHS. The suppression could be transferred to normal syngeneic animals by injection of splenic lymphoid cells obtained from animals that exhibited suppression, indicating that suppressor cells are associated with sunlight-induced systemic suppression of CHS. The immunomodulatory effect of sunlight was partially abrogated by a Mylar filter or prior application of a sunscreen containing para-aminobenzoic acid to the exposed skin. Thus, wavelengths mainly in the UVB portion of sunlight (295-320 nm) are responsible for sunlight-induced suppression of CHS, although wavelengths in the visible region may also play a role.

Animals↗
PubMed1985

Enhancement of two-stage skin carcinogenesis by exposure of distant skin to UV radiation.

Exposure of C3H/HeN mice to UV 280-320 nm (UVB) radiation induces a systemic, immunologic alteration that interferes with the rejection of highly antigenic UVB radiation-induced skin cancers. The effect of this systemic alteration, induced by ventral UVB irradiation of mice, was tested on the induction of dorsal skin tumors resulting from initiation with UVB radiation and promotion with 12-O-tetradecanoylphorbol 13-acetate (TPA). The systemic effect of UVB radiation markedly potentiated carcinogenesis at the distant site. More important, mice treated with TPA alone on the dorsal skin developed a significant number of dorsal tumors if the mice also had been exposed ventrally to UVB radiation. Treatment of dorsal skin with UVB radiation alone did not result in the development of cancers, regardless of whether the mice received ventral irradiation. These results suggest that the systemic effect of UVB radiation is exerted during the promotion phase of two-stage carcinogenesis. Furthermore, they imply that a systemic effect of UVB radiation interferes with a natural host control mechanism that ordinarily holds skin cancers in check.

Animals↗
PubMed1985

Impaired immune function in patients with xeroderma pigmentosum.

The development of contact allergy in sun-exposed skin is markedly impaired in patients with xeroderma pigmentosum as compared to the responses in healthy control subjects. The degree of this immunological impairment is directly related to the severity of the cutaneous disease. These findings raise the possibility that sunlight-induced alterations of immune function may be involved in the marked susceptibility of these patients to the development of nonmelanoma skin cancer.

Adolescent↗
PubMed1984

Systemic suppression of contact hypersensitivity by ultraviolet b radiation or methoxsalen/ultraviolet a radiation in the guinea pig.

Treatment of strain 2 guinea pigs with ultraviolet b (uvb) (280-320 nm) radiation or methoxsalen, followed by ultraviolet a (uva) (320-400 nm) radiation, decreased the contact hypersensitivity (CHS) reaction to sensitizing agents applied subsequently to unirradiated sites. The decreased reactivity could be transferred to syngeneic animals and appeared to be caused by antigen-specific suppressor T lymphocytes. Ultraviolet b irradiation of sensitized animals did not affect elicitation of CHS in unirradiated skin.

Animals↗
PubMed1984

Antigenic similarity between cells transformed by ultraviolet radiation in vitro and in vivo.

Cells of the 10T 1/2 mouse fibroblast line transformed in vitro by ultraviolet radiation are antigenically similar to those from skin cancers produced in mice by repeated exposure to ultraviolet radiation. Both types of tumor cells grew preferentially in ultraviolet-irradiated syngeneic mice relative to untreated animals, and both were recognized by ultraviolet radiation-induced tumor-specific suppressor lymphocytes. These properties were not shared by 10T 1/2 cells transformed in vitro by x-rays or 3-methylcholanthrene.

Animals↗
PubMed1984

Sun and malignant melanoma.

The incidence and mortality rates of malignant melanoma in Caucasians are increasing rapidly in many countries worldwide. Considerable circumstantial evidence suggests that exposure to solar radiation may play a role in this substantial rise in malignant melanoma. This evidence comes primarily from epidemiologic studies and from the identification of susceptible phenotypes. Despite the increasing data that implicate sunlight as an important factor in the development of certain types of malignant melanomas in humans, the role of solar electromagnetic radiation in the pathogenesis of human malignant melanomas is yet to be determined.

Aged↗