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M L Kripke

Publications and source records attributed to M L Kripke.

At least 163 records · Page 9Linked to original sources
PubMed1984

Immunological unresponsiveness induced by ultraviolet radiation.

Immunological unresponsiveness can be initiated by exposure of mice to UV radiation, followed by the introduction of certain antigens. These antigens include epicutaneously applied chemicals that induce contact hypersensitivity (CHS), and antigens that occur on skin cancers induced by UV radiation. Mice exposed repeatedly to high doses of UV radiation during UV carcinogenesis develop immunological unresponsiveness to UV radiation-induced skin cancers, which are highly antigenic. This unresponsiveness is associated with the appearance of suppressor T lymphocytes that are specific for tumors induced by UV radiation, even though these tumors express individually specific transplantation rejection antigens. Thus, the occurrence of suppressor cells with specificity for a set of non-cross-reacting tumors suggests that a common, UV-associated regulatory antigen or determinant may be present on UV-induced skin cancers. Suppression of CHS in mice by UV radiation can be induced by two different procedures. One involves applying the sensitizer directly on skin exposed to low doses of UV-B radiation and is thought to result from a direct effect of UV radiation on cutaneous Langerhans cells. The second involves application of the sensitizer to the unirradiated skin of mice or guinea pigs exposed several days earlier to a higher dose of UV-B radiation. The mechanism of the latter phenomenon is not well understood, but there is evidence that it results from an alteration of antigen presentation by splenic macrophages. Both forms of suppression are associated with the appearance of antigen-specific suppressor lymphocytes in the animals' spleens, which prevent the induction of CHS upon transfer to a normal recipient. Either or both of these pathways could be responsible for the formation of the suppressor cells involved in UV carcinogenesis. Recent studies suggest that UV radiation may also affect immunological responsiveness in humans as well as in animals. However, the extent of such alterations and the mechanisms by which they occur are still unknown.

Animals↗
PubMed1984

Mechanisms in the suppression of tumor rejection produced in mice by repeated UV irradiation.

Mice exposed repeatedly to UVB (280 to 320 nm) radiation are unable to reject highly antigenic UVB-induced skin cancers, and their lymphoid organs contain T lymphocytes that transfer this inability to nonimmune recipients. We show that the phenotype of the cells capable of transferring suppression of tumor rejection is Lyt-1+2-,Ia-. Removal of the suppressive activity of spleen cells from UVB-irradiated mice through the use of monoclonal anti-Lyt-1 antibodies resulted in a population of cells capable of mediating tumor rejection when injected into lethally x-irradiated recipients. This finding demonstrates that the inability of UVB-irradiated mice to reject skin cancers induced by UVB radiation is not due to clonal deletion, e.g., the absence of lymphocytes that are capable of recognizing and responding to antigens on these tumors, but instead is likely to depend solely on the activity of suppressor lymphocytes. The phenotype of antigen-specific suppressor lymphocytes induced by painting oxazalone on the unirradiated skin of mice exposed once to UVB radiation was Lyt-1+2-, also a finding consistent with the hypothesis that the two forms of UVB-induced immunosuppression occur by means of the same mechanism. The phenotype of suppressor cells induced in mice treated once with 8-methoxypsoralen plus UVA (320 to 400 nm) radiation, followed by painting unexposed skin with oxazalone, was Lyt-1+2+, suggesting that this treatment may activate a different suppressor pathway.

Animals↗
PubMed1984

Effects of methoxsalen plus near-ultraviolet radiation or mid-ultraviolet radiation on immunologic mechanisms.

Skin cancers induced in mice by UVB, i.e., 280-320 nm radiation, are highly antigenic. They grow progressively in UVB-irradiated hosts because of certain specific immunologic alterations that are induced in the mice. Comparative studies of the immunologic aspects of carcinogenesis by UVB or methoxsalen plus UVA, i.e., 320-400 nm radiation (PUVA), formed the basis for the following conclusions: 1) Skin cancers induced by PUVA in C3H/HeN mammary tumor virus-negative mice are not highly antigenic, in contrast to those induced by UVB; 2) PUVA-induced tumors also differ from those induced by UVB, in that they do not exhibit preferential growth in UVB-irradiated mice; 3) PUVA treatment of mice, unlike UVB, does not induce susceptibility to the transplantation of UVB-induced tumors; 4) both UVB and PUVA treatments suppress the induction of contact hypersensitivity by a mechanism that involves suppressor lymphocytes.

Animals↗
PubMed1984

Systemic suppression of contact hypersensitivity by UVB radiation is unrelated to the UVB-induced alterations in the morphology and number of Langerhans cells.

Exposure of mice to UVB (280-320 nm) ultraviolet radiation reduces contact hypersensitivity (CHS) reactions to chemicals that are applied subsequently to unirradiated skin. It also decreases the number and alters the morphology of Langerhans cells at the site of irradiation. We addressed the question of whether the systemic suppression of CHS was related to these modifications of Langerhans cells by UVB radiation. In mice treated on the dorsum with UVB radiation, the number and morphology of Langerhans cells in the unexposed areas of skin used for inducing and eliciting CHS appeared normal. Therefore, the depression of CHS could not be attributed to a depletion of Langerhans cells at the sites of application of the sensitizing agent. We also examined the correlation between alterations in Langerhans cells and systemic suppression of CHS after treatment with various types of nonionizing radiation. Treatment of mice with UVA (320-400 nm) radiation eliminated detectable Langerhans cells from the exposed skin, based on ATPase staining and electron microscopy, but did not reduce CHS; in fact, CHS was enhanced in these animals. Neither rose bengal nor eosin, in combination with visible (greater than 400 nm) radiation, affected the number or appearance of Langerhans cells, even though microscopic evidence of phototoxicity was present. However, rose bengal plus visible radiation depressed CHS reactions that were induced and elicited through unexposed skin. Depletion of Langerhans cells from dorsal skin by exposure to UVA radiation did not prevent suppression of CHS by subsequent exposure of the Langerhans cell-depleted skin to UVB radiation. We conclude that systemic suppression of CHS by UVB irradiation is not related to the numerical and morphological alterations in Langerhans cells that occur locally at the site of irradiation.

Animals↗
PubMed1983

The role of UVB radiation in the induction and elicitation of photocontact hypersensitivity to TCSA in the mouse.

Photocontact hypersensitivity (PHS) to 3,3',4',5 tetrachlorosalicylanilide (TCSA) can be induced in mice by using cyclophosphamide as an immunopotentiator. Only UVA (320-400 nm) radiation was required for both sensitization and elicitation of PHS. The reaction was successfully transferred to syngeneic mice by injecting them with lymph node cells from sensitized donors, a finding that demonstrates the immunologic nature of PHS. The presence of UVB (280-320 nm) radiation was not necessary for sensitization and did not increase PHS beyond the levels observed with UVA radiation alone. Ultraviolet radiation in the UVB range (plus a small amount of UVA radiation) from FS40 sunlamps in the dose employed did not induce statistically significant PHS to TCSA, nor did it elicit a significant response in mice sensitized with TCSA plus UVA radiation. However, treatment of mice with UVB radiation at a distant site 6 days before sensitization suppressed the induction of PHS. This suppression appeared to be analogous to the systemic suppression of ordinary contact hypersensitivity in mice by UVB radiation.

Adjuvants, Immunologic↗
PubMed1983

Systemic suppression of contact hypersensitivity in mice by psoralen plus UVA radiation (PUVA).

Treatment of mice with 8-methoxypsoralen plus longwave UV radiation (UVA, 320-400 nm) decreased their response to contact sensitizers applied subsequently to unirradiated skin. This decreased reactivity exhibited a delayed time course, it affected the afferent but not the efferent phase of the reaction, and it was associated with the development of splenic suppressor cells. These suppressor cells were antigen-specific T lymphocytes, and they prevented the induction, but not the elicitation, of contact hypersensitivity in recipient mice. In all of these characteristics, the decreased reactivity induced by treatment with psoralen plus UVA radiation (PUVA) resembled that produced by UV radiation of shorter wavelengths (less than 320 nm). These studies suggest that PUVA treatment may initiate the same sequence of cellular events as does exposure to sunlamp (UVB, 280-320 nm) radiation, leading to preferential activation of the suppressor cell pathway.

Animals↗
PubMed1983

The role of suppressor cells in the induction of murine photoallergic contact dermatitis and in its suppression by prior UVB irradiation.

Induction in mice of marked photoallergic contact dermatitis (PCD) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) with UVA (320 to 400 nm) radiation requires pretreatment with cyclophosphamide (CY). Attempts to induce photoallergic contact dermatitis without CY result in only a small degree of sensitivity, accompanied by significant net splenic suppressor cell activity. These suppressor cells are antigen specific, inhibit the induction but not the elicitation of photoallergic contact dermatitis to TCSA, and are T lymphocytes. Exposure of mice to UVB (280 to 320 nm) radiation at a site distant from that of sensitization, before CY administration and sensitization, inhibits the development of photoallergic contact dermatitis. This is analogous to the suppression of allergic contact dermatitis (ACD) observed in mice after exposure to UVB radiation; such suppression is accompanied by the formation of antigen-specific splenic suppressor cells. However, in contrast to the findings with allergic contact dermatitis, splenic suppressor cells are not detected in mice that are treated with UVB radiation before CY administration and sensitization to TCSA. This is presumably because CY prevents their formation. This provides evidence that UVB-irradiated mice have a second form of anergy that is not mediated by suppressor cells.

Animals↗
PubMed1983

Promotion of syngeneic intraocular tumor growth in mice by anterior chamber-associated immune deviation.

Regressor tumors (P91 and UV-5C25), known to express potent tumor-specific transplantation antigens, were briskly rejected when transplanted either sc or ip into syngeneic mice (DBA/2 and BALB/c, respectively). These tumors demonstrated markedly different behavior following transplantation into the anterior chamber of syngeneic mice. Tumors grew to significant masses and survived for prolonged periods within the anterior chamber of the eye. The extended growth and survival of regressor tumors in the anterior chamber (i.e. immune privilege) were abrogated by splenectomy and thus resemble anterior chamber-associated immune deviation. However, this immune privilege proved to be temporary and was superseded by complete tumor resolution. Studies of mice immunosuppressed with UV light or X-ray irradiation demonstrated that spontaneous intraocular resolution of regressor tumors was due to specific systemic immunity that not only led to intraocular tumor resolution but also prevented the spread of the primary intraocular tumor to distant organs and rendered the hosts highly resistant to secondary challenge with sc tumor inocula. The present findings were relevant to understanding human retinoblastoma, an intraocular neoplasm demonstrating a high incidence of spontaneous resolution, and will hopefully form a foundation for designing, immunotherapeutic strategies for treating human intraocular neoplasms.

Animals↗
PubMed1982

Immunoselection of tumor cell variants by mice suppressed with ultraviolet radiation.

It has previously been shown that mice exposed to ultraviolet radiation (UV) fail to reject highly immunogenic UV-induced tumors, which are regularly rejected by normal mice. The present study shows, however, that this immunosuppresion is incomplete, as UV-treated mice can still mount certain tumor-specific immune responses and reject smaller inocula of tumor cells that regularly grow progressively in athymic nude mice. Furthermore, all tumor cell lines that were reisolated from the tumor mass resulting from one tumor passage through UV-treated recipients heritably lost a tumor-specific determinant present on the parental tumor cells used for transplantation, and a large percentage of these reisolated variant tumors had changed to progressively growing tumors, in that they were no longer rejected by normal mice. In contrast, none of the tumors reisolated from passage through athymic nude mice or anti-idiotypically suppressed mice showed this change in antigenicity and progressive growth behavior. Thus, it appears that the phenotypic change in tumors reisolated from UV-treated mice was caused by immunoselection, and that the tumor-specific immunity in these mice apparently restrained the outgrowth of the parental tumor cells despite the partial immunosuppression. Because of the regularity at which tumor variants arose in the UV-treated mice after tumor transplantation, it appears that the partial immunosuppression caused by UV-treatment may have favored the outgrowth of antigenic variants from the parental tumor cell population, possibly by allowing more time for the generation of tumor variants. A similar immunoselection process might be part of tumor progression during tumor development and preferentially occur in cancer-bearing individuals showing concomitant tumor immunity.

Animals↗
PubMed1982

Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice.

Exposure of mice to ultraviolet radiation results in the development of suppressor T lymphocytes in lymphoid organs, followed by the appearance of primary skin cancers. The presence or absence of these suppressor lymphocytes determines whether or not primary cancers will develop in the ultraviolet-irradiated skin. This demonstrates the importance of immunological regulatory pathways in carcinogenesis and provides an example of immunological surveillance.

Animals↗
PubMed1982

Mechanisms of syngeneic tumor rejection. Susceptibility of host-selected progressor variants to various immunological effector cells.

The ultraviolet radiation-induced fibrosarcoma 1591 generally is rejected by normal syngeneic mice and only rarely exhibits progressive growth. We isolated five of these rare progressor tumors from normal animals to determine the selective pressures that had been exerted upon the parental tumor by normal immunocompetent hosts. We found that the variant tumor cell lines could neither induce nor be killed by tumor-specific lymphocytes, suggesting that selection had been exerted against tumor cells expressing the tumor-specific antigen. In contrast, no selection against natural killer cell activity or against nonspecific T cell-mediated immunity seems to have occurred because progressor tumor cells were highly sensitive to these types of effector cells and in fact induced these effector cells more effectively than did the parental tumor. Nude mice were found to be as capable as normal mice in generating natural killer activity in response to a challenge with progressor tumor cells, but they were unable to mount a nonspecific T lymphocyte response. This may account for the fact that the progressor tumors grew at a significantly faster rate in nude animals than in normal mice. Thus, our study shows that in this tumor system nonspecific T cell-mediated immunity may play a role in retarding tumor growth, but the absolute resistance of normal animals to progressive tumor growth critically depends upon the presence of T cell-mediated tumor-specific immunity. Furthermore, neither NK cells nor nonspecific cytotoxic T lymphocytes appear to play a role in immunoselection against this tumor in normal immunocompetent hosts.

Animals↗
PubMed1982

Immunosuppressive effects of ultraviolet (280-320 nm) radiation and psoralen plus ultraviolet (320-400 nm) radiation in mice.

Contact hypersensitivity (CHS), a cell-mediated immunologic reaction, can be induced in mice by application of a contact-sensitizing chemical to the shaved skin. Exposing the animals to UV radiation from FS40 sunlamps inhibits this immune response. This inhibition is systemic, since the sensitizer need not be applied to the irradiated site of the animal. The mechanism whereby UV radiation prevents CHS appears to involve the production of suppressor T-lymphocytes. Recent evidence suggests that UV exposure of mice alters the way in which certain antigens are processed, and this altered processing or presentation of antigen results in the activation of the suppressor cell pathway, rather than leading to immunization. Treatment of mice with a photosensitizer, psoralen, plus UV (320-400 nm) radiation also suppresses CHS systemically, but whether the cellular mechanisms are the same as those underlying the suppression from the shorter UV wavelengths remains to be determined. The possible role of these immunosuppressive events in photocarcinogenesis is discussed.

Animals↗
PubMed1982

Induction and transplantation of murine skin cancers induced by methoxsalen plus ultraviolet (320-400 nm) radiation.

Properties of skin tumors resulting from treatment of mice with ip methoxsalen plus UVA (320-400 nm) radiation (PUVA) were compared to those of skin tumors induced by UVB (280-320 nm) radiation. Repeated treatment of C3H/HeN murine mammary tumor virus-negative (C3H-) mice with PUVA produced both fibrosarcomas and squamous carcinomas that were indistinguishable morphologically from UVB-induced tumors. Fragments of 12 primary PUVA-induced tumors were transplanted into normal and immunosuppressed syngeneic recipients, and all grew progressively. In contrast, 19 primary tumors induced by repeated exposure of C3H- mice to UVB grew only in the immunosuppressed mice and not in the normal recipients. The growth of graded doses of cells from 5 PUVA-induced tumors was compared in normal and UVB-irradiated recipients. No preferential growth in UVB-irradiated mice was observed, even though this is characteristic of UVB-induced tumors. Thus PUVA-induced tumors do not appear to have the same antigenic properties as UVB-induced tumors.

Animals↗
PubMed1982

Influences of age and anatomical site on ultraviolet carcinogenesis in BALB/c mice.

Young adult BALB/c mice were mor susceptible to the induction of skin tumors from FS40 sunlamps than were 18-month-old animals. The relative contributions of tissue and host factors to this difference in susceptibility to carcinogenesis were analyzed by reciprocal grafting of skin between young and old animals, followed by repeated exposure of the grafts to UV radiation. More tumors developed in ear skin grafted to the middorsum of young recipients than in that of old recipients, regardless of the age of the skin donor. These ear skin grafts were more susceptible to tumor induction than were comparable grafts of back skin. When large areas of dorsal skin (16 cm2) were grafted to young adult mice, very old skin (greater than 2 yr) was more susceptible to tumor induction than skin that was 1 year old at the start of irradiation.

Age Factors↗