Biomedical subjects

M F Gurish

Publications and source records attributed to M F Gurish.

44 records · Page 3Linked to original sources

PubMed1983

T cell proliferative responses to a mitogen derived from Mycoplasma arthritidis are controlled by the accessory cell.

Cell-free supernatants from broth cultures of Mycoplasma arthritidis (MAS) induce vigorous proliferative responses in thymus-derived T lymphocytes from H2k or H2d strains of mice. Populations of lymphoid cells from mice of H2b, H2q, or H2s haplotypes do not respond to this stimulus. Previous studies with lymphoid cells from congenic and recombinant strains of mice indicate that the T cell proliferative response induced by MAS is controlled by a gene(s) that maps to the I-E/C subregion of the murine major histocompatibility complex (MHC). The T cell proliferative response induced by MAS is dependent upon the presence of a population of la+, radioresistant accessory cells (AC). Data presented here demonstrates that responder strain AC that have been pulsed with MAS (followed by extensive washing) induced vigorous proliferative responses in subsequently added T cell populations. Pulsing of T cells with MAS, followed by the addition of AC, however, did not result in T cell proliferation. MAS was found to stimulate (responder X nonresponder) F1 T cells to proliferate if the MAS was presented in the context of either responder or (responder X nonresponder) F1 AC; nonresponder strain AC were ineffective in this regard. Nonresponder strain T cells were found to be capable of responding to MAS if it was presented in the context of responder strain AC, even if the T cells and AC were completely allogeneic. Thus, nonresponder strain T cells mounted vigorous proliferative responses if the MAS was presented in the context of responder strain AC. Conversely, responder strain T cells did not respond to MAS presented in the context of nonresponder strain AC. In addition, lymphoid cells from a B10 leads to B6AF1 radiation bone marrow chimera were also found to be capable of responding to MAS, but only in the presence of AC that expressed cell surface determinants controlled by the I-E/C subregion. The data presented here indicate that MAS-induced T cell proliferative responses are controlled at the level of the AC by a gene(s) that maps to the I-E/C subregion of the MHC.

Animals↗

PubMed1982

Changes in antigen-presenting cell function in the spleen and lymph nodes of ultraviolet-irradiated mice.

It has been previously reported that mice exposed to ultraviolet (UV) radiation exhibit a decrease in splenic antigen-presenting cell (APC) function. The results presented here confirm this observation and further demonstrate that animals exposed daily to UV for extended periods of time (5 weeks instead of 6 days) no longer exhibit this depressed capability. In spite of the depression in splenic APC activity found in 6-day UV-irradiated mice, lymph node APC function from these same animals was elevated compared with that found in the lymph nodes from normal animals. Lymph node APC activity in animals that were splenectomized prior to the UV irradiation, however, was not enhanced over controls. Treatment of animals with a chemical irritant (turpentine) also caused a depression in splenic APC function without modifying lymph node activity. Collectively, our findings suggest that the observed decrease in splenic APC activity, found after the first week of UV exposures, may be attributable to the migration of splenic APC to peripheral lymphoid tissue which drain the site of epidermal inflammation.

Animals↗

PubMed1982

Cell-mediated immune responses to syngeneic ultraviolet-induced tumours. V. Assessment of accessory and antigen-presenting cell capabilities of normal and ultraviolet-irradiated mice in the generation of anti-tumour cytotoxic effector cells in vitro.

Draining lymph nodes (DLN) from tumour immunized mice were found to contain a population of radiation resistant, Thy 1-, Ia+ antigen-presenting cells (APC) which can stimulate normal lymphocytes to differentiate into anti-tumour CTL in vitro. APC from both normal and ultraviolet (u.v.)-irradiated tumour immunized animals were compared and exhibited equivalent functional capabilities. DLN from tumour immunized u.v.-irradiated animals were also found to contain primed T cells which could differentiate into functional anti-tumour cytotoxic T lymphocytes (CTL) with the same kinetic profile as DLN cells from normal tumour immunized mice. These results indicate that u.v. irradiation does not cause a generalized depression in either the capability of APC in u.v.-irradiated mice to process and present tumour antigens, or in the ability of u.v.-exposed animals to be primed to tumour antigens. A decrease in splenic accessory cell function was detected in animals which had received 1 week of daily 30 min u.v. exposures. The decrease in splenic accessory cell function appears to be transient, however, as no decrease in this capability was found in splenic cells obtained from animals which had received daily u.v. exposures for longer periods of time (5 weeks to 5 months). Finally, the spleens of u.v.-irradiated, tumour-bearing mice were found to contain a population of cells which could impart partial protection against tumour growth in vivo. The results of the experiments presented here indicate that normal and u.v.-irradiated animals are capable of responding similarly in the afferent phases of immune responses to syngeneic tumour antigens, and suggest that u.v.-induced T-suppressor cells mediate their immunoregulatory effects at a stage late in the generation of effective anti-tumour immune responses.

Animals↗

PubMed1981

Experimental photoimmunology: immunologic ramifications of UV-induced carcinogenesis.

The use of animal model systems to investigate the sequence of events which lead to the induction and progression of skin tumors following chronic ultraviolet light (UVL) exposure has clearly shown that the direct mutagenic effects of UVL is only one of the components involved in this process. In spite of the fact that overt carcinogenesis is only one of the many effects produced by UV light, most hypotheses as to the mechanism by which UVL can cause the mutations necessary to achieve the transformed phenotype have focused on the direct effects of UVL on DNA and the generation of carcinogenic compounds. Investigations during the last 5 yr, however, have clearly demonstrated that immunologic factors are also critically important in the pathogenesis of UV-induced skin cancers. A complete understanding of UV-carcinogenesis must therefore consider the mechanisms which allow the transformed cell to evade immunologic rejection by the host in addition to those aspects which deal with conversion of a normal cell to a cancer cell. It is the object of this review to provide both a historical account of the work which established the immunologic consequences of chronic UVL exposure and the results of recent experiments designed to investigate the kinetics and mechanisms by which UVL affects the immunologic apparatus. In addition, a hypothetical model is presented to explain the sequence of events which ultimately lead to the emergence of the suppressor T-cells which regulate antitumor immune responses.

Animals↗

PubMed1981

The effect of various sunscreen agents on skin damage and the induction of tumor susceptibility in mice subjected to ultraviolet irradiation.

Sunscreen preparations containing various chemical UV absorbers, para-aminobenzoic acid (PABA), 2 PABA derivatives, benzophenone or a combination of these were topically applied to the backs of C3H/HeN mice prior to their being irradiated with ultraviolet light in the UVB range. In all cases this treatment was effective in preventing the pathological skin changes associated with UVB irradiation. Histological evaluation of skin biopsies from mice treated with the sunscreen preparations and UVB irradiation showed little or no difference from normals in amount of hyperplasia, melanization or parakeratosis present. These histologic changes were observed in animals receiving UVB irradation in the absence of any sunscreen agent. Pretreatment with the various sunscreen agents did not, however, prevent the induction of tumor susceptibility as measured by the sustained growth of a UV-induced tumor which is immunologically rejected in normal syngeneic mice. These data show a clear distinction between the effects of UVB irradiation leading to histological changes in the epidermis and those leading to the state of tumor susceptibility in mice. The distinction was further corroborated by the finding that epidermal hyperplasia induced by repeated applications of croton oil had no significant enhancing or inducing effects on the induction of tumor susceptibility. In addition, the induction of tumor susceptibility. In addition, the induction of tumor susceptiblity is not due to wavelengths of light less than 320 nm since this effect was abrogated when the UVB radiation was filtered through glass. Possible mechanistic differences between the tumor susceptiblity generated in UVB and photoprotected UVB irradiated animals were observed, however, when we attempted to adoptively transfer the state of tumor susceptibility to normal animals. While it was readily transferable with splenic lymphoid cells from UVB irradiated animals, all attempts to transfer the tumor susceptibility from photoprotected animals have, to date, been unsuccessful.

Animals↗

PubMed1981

Relationship between epidermal Langerhans cell density ATPase activity and the induction of contact hypersensitivity.

Langerhans cells have been implicated as playing a crucial role as antigen-processing cells in the induction of positive immune responses to antigens presented through the skin. We have investigated the effects of carcinogenic doses of UVB-irradiation, psoralen plus UVA light (PUVA), PABA containing sunscreen preparations, and topically applied corticosteroids on both Langerhans cell densities and immunologic responsiveness to contact sensitizers applied to the treated site. The data presented demonstrate that UV-irradiation of skin or topical application of corticosteroids can create a local milieu in which DNFB cannot function as an effective stimulator of contact hypersensitivity. Further, we have shown that the effect induced by UV light is reversible, does not appear to be related to the numerous tissue destructive effects of UVB-irradiation, and that the correlation with the density of ATPase-positive cells is not absolute.

4-Aminobenzoic Acid↗

PubMed1981

The effects of ultraviolet irradiation on the generation of anti-tumor cytotoxic effector cell responses in vitro.

The effects of irradiation of lymphoid cells in vitro with ultraviolet (UV) light were studied using radiation sources that are widely used both in the study of photocarcinogeneic mechanisms and by commercial tanning parlors (FS40 sunlamps). Low doses of direct exposure of cells was found to abrogate the differentiation events that lead to the generation of functional cytotoxic T lymphocytes (CTL). UV irradiation of cells in vitro induces alterations that, although not immediately obvious, lead to cell death during the next several days in tissue culture. Energy titration experiments demonstrated that both primed T cells and accessory cells were sensitive to the effects of direct UV-exposure; T cells were found to be much more sensitive than accessory cells. A 90% decrease in CTL generation could be affected with as little as 10 sec of UV exposure. These effects appear to be caused by wavelengths in the UVB range (280 to 320 nm), since exposure of cells to much higher doses of energy in the UVA range (320 to 400 nm) were not inhibitory. The spectrum of wavelengths in the UV region is large (200 to 400 nm). The data presented here demonstrate that it is overly simplistic to assume that all wavelengths in the UV spectrum mediate their effects via identical mechanisms. Furthermore, the wavelengths at which a given amount of energy is emitted appears to be much more important than the absolute amount of energy (in joules) which biologic systems are subjected.

Animals↗

PubMedDate not supplied

Induction of antibodies to pseudorabies virus by immunization with antiidiotypic antibodies.

We have induced the expression of high titres of antibodies to pseudorabies virus (PRV) by immunization of A/J mice with polyclonal antiidiotypic antibodies directed against each of 2 BALB/c monoclonal, neutralizing anti-PRV antibodies. The anti-PRV antibodies induced by one of the antiidiotypic antibody preparations had an affinity for PRV comparable to that of the original monoclonal antibody. Mice immunized with antiidiotypic antibodies were protected to a significant degree against viral infection but the degree of protection was lower than that conferred by passive transfer of monoclonal neutralizing antibody or by immunization with attenuated virus.

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