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L K Roberts

Publications and source records attributed to L K Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1986

Involvement of prostaglandins in the immune alterations caused by the exposure of mice to ultraviolet radiation.

Our study was designed to analyze the possible involvement of prostaglandins in the mechanisms responsible for the depressions in contact hypersensitivity (CH) responsiveness observed in UVR-exposed animals. Low-dose UVR-exposed animals were found to exhibit a depressed capacity to elicit CH responses after hapten application to irradiated (devoid of Langerhans cells) or UVR-protected (normal Langerhans cells) dorsal skin surfaces. Normal responsiveness was observed in low-dose UVR-exposed animals sensitized through unirradiated ventral skin surfaces. Indomethacin treatment of low-dose UVR-exposed animals (to inhibit prostaglandin synthesis in vivo) caused a retention in the capacity to respond normally to CH induction to haptens applied to the nonirradiated, but not to irradiated, dorsal skin surfaces. High-dose UVR-exposed animals, which normally exhibit a depression in responsiveness to hapten sensitization, retained a normal capacity to elicit CH responses if treated with the drug indomethacin. These findings implicate prostaglandins in the pathogenesis of the immunologic hyporesponsiveness, observed in low- and high-dose UVR-exposed animals. Our studies also determined that under all experimental conditions where animals were contact sensitized through nonirradiated skin sites, CH-effector cells could be found in the draining lymph nodes. No CH-effector cells were observed in the lymph nodes of mice that were contact sensitized directly through irradiated skin sites. It was also found that the spleens of both UVR-exposed and normal animals contained adoptively transferrable suppressor cells subsequent to hapten application. This demonstration of CH-effector and CH-suppressor cells in both normal and UVR-exposed animals did not directly relate to the potential of the donor animals to elicit a CH response.

Animals↗
PubMed1986

Characterization of a cloned ultraviolet radiation (UV)-induced suppressor T cell line that is capable of inhibiting anti-UV tumor-immune responses.

Ultraviolet radiation (UV) is a potent carcinogen for the induction of skin tumors. In this regard, UV represents a unique carcinogenic agent, in that depending on the dosage and conditions of administration it can function as either a complete carcinogen, a carcinogenic promoting agent, or an immunologic modulator of anti-tumor rejection responses. The immunologic modulatory activity of UV has been demonstrated in numerous studies. These studies have shown that subcarcinogenic doses of UV induce a population of suppressor T lymphocytes (Ts cells) that allow for the emergence and progression of UV-induced tumors. Although the phenotypic and functional properties of these cells have been established, it was unclear as to whether the UV-induced Ts cell population consisted of multiple Ts cell clones able to recognize a range of unique tumor antigens or a limited number of Ts cell clones with functional specificity directed toward a common tumor-associated antigen (TAA). To address this question, an interleukin 2-dependent, UV-induced cloned Ts cell line was derived, by limiting dilution without exogenous antigen stimulation, from the splenic T cell population of a C3H mouse that had been exposed to a subcarcinogenic dose of UV. This Ts cell line, designated UV2.10, was selected for its ability to suppress the in vitro differentiation of cytotoxic T cells from the draining lymph nodes of UV-induced tumor-immune mice. When transferred into non-UV-irradiated syngeneic mice, which normally reject a UV-induced tumor implant, the UV2.10 cells rendered their hosts susceptible to the growth of a battery of UV-induced tumors. Although capable of suppressing in vitro and in vivo UV-induced tumor-immune responses, UV2.10 cells did not inhibit the elicitation of contact hypersensitivity responses, the rejection of allogeneic skin grafts, responses, the rejection of allogeneic skin grafts, or the rejection of allogeneic UV-induced tumors. These data suggest that the cloned UV2.10 Ts cell line possesses functional antigenic specificity that may be limited to the regulation of immune responses that are directed toward the TAA expressed by syngeneic UV-induced tumors. Employing monoclonal antibodies and FACS analysis, the cell surface phenotype of the UV2.10 cell line was determined to be: Thy-1.2+, Lyt-1-, Lyt-2+/- (dim), L3T4a-, I-A/E-, and I-J+. This cell surface phenotype is indicative of a suppressor T cell. These data lend further support to the hypothesis that the UV-induced Ts cell population is clonal in nature and functions through its ability to recognize a common TAA(s) that appears to be expressed by virtually all UV-induced tumors.

Animals↗
PubMed1986

Description of and treatment to inhibit the rejection of human split-thickness skin grafts by congenitally athymic (nude) rats.

Gradual rejection of topically engrafted human split-thickness skin grafts (HSTSG) occurred in greater than 90% of congenitally athymic (nude) rats between 21 and 42 days of grafting. Engraftment and rejection of HSTSG is accompanied by a partial restoration of some cell-mediated immune components, the mixed lymphocyte response and lysis of human target cells. Histologic features of the rejection process were those seen in a host-versus-graft reaction. Immunofluorescent analysis of skin undergoing rejection demonstrated IgG at the basement membrane zone in most grafts. Nude rats rejecting HSTSG had circulating IgG which bound to the basement membrane zone and blood vessels of human skin. Nude rats treated with cyclosporine injections for 21 days had an enhanced survival of HSTSG, 120 or more days.

Animals↗
PubMed1986

Immunological consequences of ultraviolet radiation exposure.

Depending on the dose and conditions of administration, ultraviolet radiation (UVR) can function as either a complete carcinogen, a co-carcinogenic agent, or an immunologic modulator. Although much is known about its carcinogenic properties, only recently have investigations been aimed at defining the mechanisms by which UVR mediates its effect on the immune system. The objective of this article is to present the necessary background and results of recent studies that provide the basis for defining some of the local and systemic effects that UVR has on an individual's immunologic potential. This discussion focuses on: the histologic alterations in the skin and draining lymph nodes, the changes in lymphocyte localization, the increased release of the immunologic (and physiologic) mediator ETAF/IL-1, and the induction of antigen-specific immunoregulatory circuits that occur subsequent to UVR exposure. It is our hypothesis that the detrimental effects that UVR has on the host's immunologic competence may represent a normal defense mechanism to protect the individual against the adverse consequences of chronic inflammatory stimuli. In this regard, a better understanding of photoimmunology may lead to the development of more effective means of immunologic modulation for altering the clinical course of various human diseases that are either immunologically mediated, photoinduced, or responsive to phototherapy.

Cell Transformation, Neoplastic↗
PubMed1985

Regulation by the skin of lymphoid cell recirculation and localization properties.

The existence of epidermal Langerhans cells, Ia-positive dermal dendritic cells, lymphocytes which can demonstrate epidermitropism, and keratinocytes capable of secreting Interleukin-1-like molecules, each support the concept that skin can function as an immunologic organ. Such conclusions are further strengthened by the knowledge that both afferent and efferent immune responses can take place exclusively within the skin. The purpose of our study was to evaluate the ability of skin to regulate lymphoid cell recirculation and localization properties. The use of ultraviolet radiation as an exogenous stimulus resulted in a pronounced redistribution of antigen-presenting cells from central (spleen) to peripheral (skin and lymph node) lymphoid tissues as well as marked increase in the rate of lymphocyte entry into skin draining lymph nodes. This latter condition was due to elevations in the quantitative levels of high endothelial venules present within the peripheral lymph nodes. The ability of epidermal keratinocytes to express Class II molecules is known to be associated with a number of skin diseases. However, the functional significance of this phenomenon is unknown. The results of our studies, employing a nude mouse model, indicate that the expression of Class II molecules by keratinocytes facilitates the movement of Langerhans cell precursors into the epidermis and may also function to enhance lymphocyte entry into the skin. We conclude that nonlymphoid components resident within the skin can influence essential aspects of the adaptive immune response through the production of soluble factors (e.g., Interleukin-1 or through the cellular expression of Class II molecules.

Animals↗
PubMed1985

Characterization of the metabolism inhibition antigen of Mycoplasma arthritidis.

The Mycoplasma arthritidis antigen(s) responsible for eliciting metabolism-inhibiting antibodies in rabbits has been partially characterized. Metabolism-inhibiting activity was absorbed from rabbit antisera by intact M. arthritidis cells and membranes but much less so by the soluble cytoplasmic fraction, indicating that the antigen is located on the outer membrane surface. It was stable to periodate and lipid extraction but labile to heat and proteolytic enzymes, indicating that it is protein in nature. Finally, it is most likely a tightly bound integral rather than a peripheral membrane protein, since it was not extracted by low-ionic-strength solutions or by the nonionic detergents Triton X-100, Nonidet P-40, and Tween 20. It was solubilized by both the anionic agent sodium deoxycholate and the zwitterionic detergent Zwittergent. Two two monoclonal antibodies with metabolism-inhibiting activity were produced. One recognized a 45,000-dalton surface protein; however, the other recognized an antigen which is probably of cytoplasmic origin, indicating that more than one cell component may be involved in the metabolism-inhibiting antibody response.

Antibodies, Monoclonal↗
PubMed1985

Correlation between the inducible keratinocyte expression of Ia and the movement of Langerhans cells into the epidermis.

A direct correlation between the induced expression of Ia by the host keratinocytes and the infiltration of donor Langerhans cells (LC) into the epidermis was demonstrated in athymic (nude) BALB/c mice that received an adoptive transfer of lymphoid cells from normal semi-syngeneic donors. Neither keratinocyte expression of Ia nor donor LC movement into the epidermis was observed in BALB/c recipients of lymphoid cells from allogeneic C3H nude mice. Further evidence for this relationship was provided by experiments in which the keratinocytes of BALB/c nude mice were induced to express Ia by the injection of normal mouse serum (NMS). By this procedure it was shown that LC precursors derived from allogeneic C3H nude donors were able to infiltrate the epidermis when adoptively transferred into BALB/c nude recipients whose keratinocytes had been induced to express Ia by the simultaneous injection of NMS. These findings suggest that keratinocytes through their expression of Ia may function to facilitate the movement of LC into the epidermis.

Animals↗
PubMed1985

Correlation between keratinocyte expression of Ia and the intensity and duration of contact hypersensitivity responses in mice.

Langerhans cells are the only cells within the epidermis that normally express immune response-associated antigens (referred to as Ia in mice and HLA-D in humans). However, in the epidermis of patients with allergic contact dermatitis or individuals undergoing a delayed-type hypersensitivity response, the keratinocytes at the reaction site are induced to express HLA-DR. In this study the inducible expression of Ia by the keratinocytes of mice was found to be directly correlated with the intensity and duration of experimentally induced contact hypersensitivity (CH) responses. During a CH response in animals that were sensitized on the belly and challenged on the ear with the contact-sensitizing (CS) agent oxazolone, the keratinocytes in the challenged, but not the unchallenged, ear were induced to express Ia. In comparison with animals that were sensitized and challenged at different sites, an intensified expression of Ia by the keratinocytes was associated with a twofold increase in ear swelling in mice that were sensitized and challenged with oxazolone at the same site. Curiously, the challenge of oxazolone-sensitized ears with dinitrofluorobenzene (an unrelated CS agent), croton oil (a nonspecific inflammatory agent), or acetone/olive oil (a noninflammatory agent) also induced both a marked keratinocyte expression of Ia and an enhanced CH response. These results suggest that residual antigen at the original sensitization site may be mobilized to function as the challenge stimulus to elicit a CH response, in association with keratinocyte expression of Ia, when CS-sensitized skin is perturbed with a nonspecific agent. Further evidence of an association between CH responsiveness and keratinocyte expression of Ia came from the following observations. First, the magnitude and duration of a CH response was markedly increased in pertussis toxin (PT)-treated mice. These enhanced responses were associated with intense Ia expression by the keratinocytes in the epidermis at the reaction site. Because PT is known to have an adjuvant effect on delayed-type hypersensitivity reactions, as well as to alter the normal regulatory mechanisms associated with this type of response, it is possible that Ia+ keratinocytes play a synergistic role in the enhanced CH responses that are observed in PT-treated animals. Second, a direct correlation between keratinocyte expression of Ia and CH responsiveness was observed in athymic nude mice that were challenged with oxazolone after receiving an adoptive transfer of lymphoid cells from oxazolone-primed normal syngeneic donors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adjuvants, Immunologic↗
PubMed1984

Identification and characterization of mononuclear phagocytes isolated from rat testicular interstitial tissues.

Rat testicular interstitial tissues contain numerous mononuclear phagocyte-like cells. Dispersed testicular tissues are allowed to settle onto a glass substrate and the strongly adherent cells are identified as the same cells that have been described in vivo, based on the retention of an in vivo marker (plutonium). These putative testicular intersitial tissue macrophages (TIMs) have adhesion and cell surface features characteristic of mononuclear phagocytes, as determined by scanning electron microscopy. Immediately after isolation from testicular tissues, TIMs show a strong staining reaction for nonspecific esterase. These cells have Fc and complement receptors and some express Ia cell-surface antigens. About two thirds of the TIMs phagocytose sheep red blood cells and most of the cells are capable of nonspecific phagocytosis of polystyrene beads. This study demonstrates that the phagocytic cells found in testicular interstitial tissues have morphological, histochemical, phagocytic, and immunological properties characteristic of functionally active mononuclear phagocytes. These results suggest that these resident mononuclear phagocytes may play a role in immune-related functions in the testis.

Animals↗
PubMed1984

Experimental ultraviolet radiation carcinogenesis: I. Relationship of the major histocompatibility complex to tumor latency and immunogenecity.

The induction of skin tumors by ultraviolet radiation (UV) was compared concurrently in 3 inbred mouse strains (BALB/c, C3H, and C57BL/10) and 7 related H-2 (major histocompatibility complex) congenic strains of mice. The latency period for UV-tumor induction was observed to be shorter in BALB/c mice compared with that in C3H and C57BL/10 animals. Similarly, tumor latency periods in the different H-2 congenic mouse strains tested were comparable to those of their related background strain. The proportion of squamous cell carcinomas to spindle cell fibrosarcomas, as well as the ratio of progressor and regressor tumors, as determined by their ability to grow when transplanted into normal syngenic mice, were comparable for those strains of mice that shared common genetic backgrounds. Interestingly, for all strains of mice analyzed UV-regressor and UV-progressor tumors were found to arise randomly throughout the latency period. These studies suggest that, at least for the three parameters tested, genes or gene products encoded within the major histocompatibility complex do not influence either latency period, histologic type or immunogenicity of UV-induced skin tumors.

Animals↗
PubMed1983

Establishment of a continuous T cell line capable of suppressing anti-tumor immune responses in vivo.

This report describes the induction, phenotypic characteristics, and functional properties of a continuous suppressor T cell line. This cell line, UV1, is capable of suppressing anti-tumor immune responses both in vivo and in vitro. The UV1 cell line was derived from a T cell-enriched (nylon wool nonadherent, Ia-negative panned fraction) spleen cell population from a ultraviolet radiation-(UV) exposed BALB/c Wehi mouse. By using an in vivo functional assay designed to demonstrate tumor-specific UV-induced suppressor T lymphocyte (Ts cell) activity, it was found that UV1 cells were capable of rendering normal syngeneic mice susceptible to the growth of UV-induced regressor tumors. In addition to their suppressive activity in vivo, UV1 cells displayed in vitro suppressive activity by blocking the differentiation of cytotoxic T cells from the draining lymph nodes of UV-tumor immunized animals. By flow cytometric analysis it was determined that UV1 cells expressed a number of T lymphocyte differentiation antigens and did not express any detectable amounts of surface immunoglobulin, I-A or E/C antigens, Fc receptors, or macrophage antigens. These data suggest that the UV1 cell line may be representative of the UV-induced Ts cell population and provide a potential means for studying UV-induced immunoregulatory mechanisms in greater detail.

Animals↗
PubMed1983

Expression of Ia antigen on epidermal keratinocytes after the grafting of normal skin to nude mice.

During the course of experimentation designed to evaluate the migration of host Langerhans cells (LC) into normal skin grafted onto nude mice, we observed that the epidermal cells of these grafts were induced to express la determinants solely of graft origin. The data presented herein indicate that the expression of la by normal epidermal cells correlates with the infiltration of host LC into the graft. This la expression is restricted to the keratinocytes within the epidermis of the grafted skin, is first observed 7 to 9 days post-grafting, and persists within the grafted skin for greater than 12 wk. The induction of la expression by keratinocytes appears to be the result of the environment that is provided by the nude mouse host and is independent of both passenger lymphocytes within the skin graft and allogeneic differences between graft and host. We strongly believe that these studies provide the basis for the development of an experimental animal model system for investigating the potential role that la expression by epidermal cells may play in enhancing the immune response to antigens encountered in the skin.

Animals↗
PubMed1983

Enhanced tumorigenicity of cloned UV-regressor tumor lines following selected in vivo and in vitro manipulations.

Passage of cloned ultraviolet (UV) radiation-induced fibrosarcomas with regressor phenotype through 500-rad-irradiated syngeneic mice resulted in their conversion to transplantable progressor tumors. A similar conversion in tumorigenic phenotype (regressor leads to progressor) was found to be inducible in vitro by coculturing a cloned regressor tumor with normal splenocytes, but not with splenocytes from tumor-immune or UV-irradiated animals. Recloning of regressor and converted progressor tumor lines yielded regressor and progressor phenotype subclones, respectively, suggesting a degree of stability in their growth phenotype. Although all of the cloned progressor tumors tested were found to be cross-reactive with related regressor tumor lines, suggesting that related clones share a similar tumor-specific transplantation antigen, the progressor clones appeared to be less immunogenic than the regressor clones. Potential mechanisms that influence this conversion in tumorigenic phenotype are discussed.

Animals↗