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J J Hooks

Publications and source records attributed to J J Hooks.

At least 55 records · Page 3Linked to original sources
PubMed1990

Cytokine-mediated activation of a neuronal retinal resident cell provokes antigen presentation.

The retinal pigment epithelial (RPE) cell has long been considered an important regulatory cell, maintaining physiological and structural balance within the retina. We have previously shown that the RPE cell may also be important in autoimmunity and transplantation. These cells can be induced by cytokines to express MHC class II Ag in ocular inflammatory and autoimmune conditions. In this report we show that isolated rat RPE cells can be induced to express class II Ag following incubation with rat rIFN-gamma. The ability of RPE cells to present Ag was determined by both T cell proliferation assays and IL-2 production. Only the Ia-positive RPE cells can present retinal Ag (S-Ag and interphotoreceptor-binding protein) to specifically sensitized rat Th cells. Moreover, the ability of chloroquine to inhibit this activity suggests that the RPE cell is also capable of processing Ag prior to Ag presentation. These studies indicate that cytokine-mediated activation of RPE cells may be a basic component of ocular immunity and an important aspect of RPE cell transplantation.

Animals↗
PubMed1990

Evaluation of Ia expression in rat ocular tissues following inoculation with interferon-gamma.

It is becoming increasingly clear that IFN-gamma is a potent immunoregulatory protein which influences MHC class II (Ia) antigen expression and cellular functions of B cells, T cells, NK cells and macrophages. During the past 5 yr our laboratory has provided evidence that IFN-gamma modulates class II antigens on retinal cells (retinal pigment epithelial cells, endothelial cells) and is localized within the eye during human inflammatory conditions. In this study we evaluate the direct effect of IFN-gamma on ocular tissue. Lewis rats were inoculated intravitreally or under the retina with either recombinant IFN-gamma (20,000 U) or saline. At 2 hr, 1, 2 and 6 days postinoculation, the eyes were removed and frozen sections were evaluated by immunocytochemical staining with monoclonal anti-Ia antibodies and an irrelevant monoclonal anti-T cell antibody. Saline treated tissue and tissue removed 2 hr after IFN-gamma inoculation showed no significant staining for Ia antigens. However, eyes evaluated 24 hr after IFN-gamma inoculation revealed Ia expression on a variety of ocular cells localized in the conjunctiva and anterior segment, such as conjunctival epithelium, keratocytes, iris epithelium, ciliary epithelium and choroidal cells. In the retina, retinal pigment epithelial (RPE) cells were Ia positive only when IFN-gamma was injected directly under the retina. In conjunction with Ia expression, two striking changes were noted. An iritis was seen and infiltrating cells were detected in the inner retinal layers. Both of these phenomena have been observed in certain inflammatory eye diseases. These studies clearly substantiate the concept that IFN-gamma can regulate class II antigens in the eye and thus may perpetuate immune reactivity in this site.

Animals↗
PubMed1990

Interferon-gamma enhances the expression of retinal S-antigen, a specific neuronal cell marker.

Interferon-gamma (IFN-gamma) is a potent lymphokine which can modify a variety of cellular processes. One of the mechanisms involved in these processes is the ability of IFN-gamma to alter the regulation and expression of cellular proteins. Using analytical flow cytometry, we show that recombinant human IFN-gamma can enhance the expression of retinal S-antigen in retinoblastoma cells. This enhancement was selective since two other retinal cell proteins, interphotoreceptor binding protein (IRBP) and photo-6, were not affected by IFN-gamma treatment. Retinal S-antigen plays an important role in vision and is one of the retinal proteins capable of inducing an inflammatory eye disease called experimental autoimmune uveitis. These studies therefore demonstrate an important role for this lymphokine, that is, the enhanced expression of a neuronal cell protein. This finding may also identify additional mechanisms by which IFN-gamma may participate in immunopathologic events in nervous tissue.

Antibodies, Monoclonal↗
PubMed1990

Murine coronavirus induces an acute and long-lasting disease of the retina.

The ability of the coronavirus mouse hepatitis virus, strain JHM, to grow in the retinas of BALB/c mice was examined. Inoculation into the vitreous chamber produced significant changes. Immunoperoxidase staining of frozen sections with either monoclonal or polyclonal antiserum revealed coronaviral antigens in the iris, ciliary body, and a few ganglion cells on day 1. The retinal pigment epithelial cells began expressing viral antigen on day 2 and large amounts of antigen were present in these cells on day 3. Viral antigens were detected in all layers of the neural retina by day 6 and were absent after day 7. Infectious virus was recovered from retinas harvested at 5 days. The drop in viral antigen expression was correlated with an elevation in virus-specific antibody; the latter began to rise on day 5 and plateaued after day 8. In hematoxylin and eosin- or periodic acid -Schiff-stained sections of virus-inoculated left eyes, but not mock-inoculated right eyes, lesions spanning all layers of the neural retina were detected by day 3. Subsequently abnormalities in retinal pigment epithelial cells appeared, sometimes around the entire circumference of the retina. Significant retinal abnormalities, notably photoreceptor degeneration, persisted through 6 weeks. These results demonstrate that coronaviruses can cause acute infection of the posterior pole of the eye, resulting in only a mild inflammatory response and long-lasting disease. This murine disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in man.

Acute Disease↗
PubMed1989

Development and characterization of monoclonal antibodies directed against the retinal pigment epithelial cell.

The retinal pigment epithelium consists of a unicellular layer of neuroepithelial cells that are essential for the maintenance of normal function of the neural retina. In order to evaluate more critically this cell in health and disease, we prepared monoclonal antibodies against human retinal pigment epithelial (RPE) cells. Balb/c mice were immunized with human RPE cells. Spleen cells were fused with myeloma cells and resultant hybridomas were selected for antibody production. Supernatants were assayed by immunoperoxidase on frozen sections of human eye tissues. Two hybrids were cloned and ascites were generated in mice. These IgG antibodies react only with RPE cells and show no cross-reactivity with other cells in the eye or with human brain, kidney, skin, salivary glands, lymphocytes or monocytes. These antibodies recognize cell surface molecules that are highly conserved since they can be found in man, monkey, rat, cow, chicken and frog. SDS gel electrophoresis and immunoblot analysis showed that one of the antibodies reacted with a 42,000 MW polypeptide. Evaluation of the developing rat retina revealed that the epitopes are not detected at birth, are weakly present at day 6 and are highly recognized by day 9. These immunoglobulins will allow us to evaluate RPE cells in disease (proliferation, migration) and to probe the bioregulatory functions (phagocytosis, vitamin A transport) of these cells.

Animals↗
PubMed1988

Coexpression of neuronal, glial, and major histocompatibility complex class II antigens on retinoblastoma cells.

This study identifies the presence of major histocompatibility complex class II antigens on retinoblastoma cells. In addition, the modulation of HLA-DR by interferon-gamma as well as the preferential expression of this major histocompatibility complex molecule over HLA-DQ is described. Double labeling experiments revealed that HLA-DR antigen is shared concomitantly with cells of glial and neuronal character. Investigations such as these underscore the possibility that expression of major histocompatibility complex class II antigens may function as immunological components in the host or play a role in the cellular differentiation of these tumor cells.

Antigens↗
PubMed1988

Anti-Ia antibody diminishes ocular inflammation in experimental autoimmune uveitis.

An experimental model of inflammatory eye disease, experimental autoimmune uveitis (EAU), was established by injecting rats in the footpad with S-antigen in complete Freund's adjuvant. This model system was used to evaluate the role of major histocompatibility complex (MHC) class II antigens (Ia) in the pathogenesis of this T cell mediated disease. One day prior to S-antigen priming, rats were injected with either anti-Ia antibodies or with mouse ascites. Clinical and histopathological analysis of eyes from rats treated with anti-Ia antibody showed less ocular inflammation as well as a delay in onset of EAU when compared to controls (p = 0.01). Furthermore, immunocytochemical evaluation demonstrated that tissue obtained from animals receiving anti-Ia therapy also expressed less Ia antigen, as well as a diminution in the number of infiltrating macrophages and lymphocytes. These data show that anti-Ia treatment significantly modifies the course of EAU in the rat. In addition, this study suggests that MHC class II antigen expression may be involved in the initiation and continuation of immune responses that results in ocular inflammatory diseases.

Animals↗
PubMed1988

Identification of the lymphokines, interferon-gamma and interleukin-2, in inflammatory eye diseases.

The exact pathogenic mechanisms involved in autoimmune and inflammatory eye diseases are not known. However, studies during the past few years indicate that a T cell infiltrate, T cell sensitization to retinal antigens and expression of major histocompatibility complex (MHC) class II antigens are associated with this process. In this report we show that the lymphokines, IL-2 and IFN-gamma, are present in the human eye during inflammatory and autoimmune diseases. The presence of these lymphokines is associated with a lymphocyte infiltrate, predominantly of T cell origin, and with the expression of MHC class II antigens on both the infiltrating cells and ocular resident cells, that is, retinal pigment epithelial (rpe) cells and retinal vascular endothelial cells. Furthermore, in vitro studies demonstrate that IFN-gamma can enhance the expression of the HLA-DR determinant on both of these cell types. These observations suggest that lymphokine induced class II antigen expression may serve as a local amplification system in autoimmune and inflammatory eye diseases. A better understanding of the role of lymphokines in the mechanisms involved in the development of autoimmunity and inflammation may be beneficial in the treatment of these diseases.

Adult↗
PubMed1987

Retinal vascular endothelium expresses fibronectin and class II histocompatibility complex antigens in experimental autoimmune uveitis.

To analyze the role of the retinal vascular endothelial cells in the development of experimental autoimmune uveitis (EAU), we studied the presence of Ia antigen and FN in retinal vessels of Lewis rats immunized with retinal S antigen. Immunopathologic studies were performed on frozen tissues obtained during various stages of the disease. Our results show that Ia antigen was not present in the normal rat retina, and there was very little FN present in a few retinal vessels. One to two days prior to the histologic and clinical onset of EAU, FN was found to be increased in the retinal vessels. Ia antigen was found to be present in the retinal vessels coincident with the first signs of cellular infiltration. During the stage of maximal cellular infiltration, FN was present diffusely throughout the retina, as well as in the subretinal space, and Ia antigen was found diffusely in the cellular infiltrate. Therefore, FN and Ia antigen reflect the immunomodulation of vascular endothelial cells in EAU, which may be very important in the pathogenesis of retinal S antigen-induced uveitis. Two possible mechanisms for the role of the activation of the retinal vascular endothelium in the development of retinal inflammation in uveitis are discussed.

Animals↗
PubMed1987

Effect of cyclosporin A (CyA) on the immunopathological lesion of the labial minor salivary glands from patients with Sjögren's syndrome.

Labial minor salivary gland biopsy specimens from 14 patients with Sjögren's syndrome treated either with cyclosporin A (CyA) or placebo (5 mg/kg body weight day for six months) were studied to determine T lymphocyte subsets and HLA-DR antigen expression using the avidin-biotin-peroxidase technique. In all CyA treated patients we observed a decrease in the number of T lymphocytes and in the number of T helper cells, while the percentage of T suppressor cells and B cells was the same in both treated and untreated groups. It was also shown that the HLA-DR antigen expression on the epithelial cells was eliminated in the CyA treated patients. These findings suggest that the HLA-DR antigen expression on the epithelial cells is the result rather than the triggering factor of this T cell mediated process and is probably related to decreased lymphokine production by activated T lymphocytes.

Cyclosporins↗
PubMed1986

Expression of HLA-DR antigen on retinal pigment epithelial cells in retinitis pigmentosa.

Class II (HLA-DR) antigens are cell surface molecules that play a major role in the initiation and perpetuation of immune responses. Although most cells do not constitutively express class II antigens, selected cells can be stimulated to do so in some immunologically mediated disorders. When retinal pigment epithelial cells were evaluated by either immunoperoxidase or immunofluorescent staining of frozen eye sections from normal individuals, HLA-DR antigens were not detected. In contrast, retinal pigment epithelial cells from two patients with retinitis pigmentosa did express HLA-DR antigens. These findings demonstrated that at some time during the course of retinitis pigmentosa, the retinal pigment epithelial cell is activated to express HLA-DR.

Aged↗
PubMed1986

HLA-DR antigens on retinal pigment epithelial cells from patients with uveitis.

The pathogenic mechanisms involved in immunologically associated ocular diseases are not clearly understood. To further evaluate these types of disorders, we examined the expression of HLA-DR antigen on eye sections from normal individuals and five patients (six eyes) with ocular inflammation (sympathetic ophthalmia and chronic uveitis). Using immunoperoxidase staining technique and the complement-mediated cytotoxicity assay, we detected the presence of HLA-DR antigens on retinal pigment epithelial (RPE) cells from uveitic eyes. In contrast, HLA-DR antigen was not detected on RPE cells from normal ocular tissue. Our study shows that during the course of human ocular inflammatory disorders, the RPE cell is activated to express HLA-DR antigens. This antigen expression may be important in the initiation and/or perpetuation of immune reactivity in the eye.

Adolescent↗
PubMed1986

HLA-DR expression by labial minor salivary gland tissues in Sjögren's syndrome.

Minor salivary gland biopsy specimens from patients with Sjögren's syndrome (primary and secondary) and from normal controls were examined with the four step biotin-avidin-immunoperoxidase assay. The composition of the infiltrating cells was similar in patients with both primary and secondary Sjögren's syndrome, consisting primarily of T lymphocytes with predominance of T helper/inducer cells. B lymphocytes (Leu-14) were approximately 20-35% of the infiltrating lymphocytes, while only a few OKM1 (monocytes/macrophages) cells and Leu-7+ (natural killer; NK) cells were observed. The majority of infiltrating lymphocytes expressed HLA-DR antigens. In the biopsy specimens of the controls there were no infiltrates; the scattered lymphocytes, however, were also predominantly T lymphocytes. Finally, the glandular epithelial cells (ducts and acini) were inappropriately expressing HLA-DR antigens, in contrast with controls where minimal HLA-DR expression was found.

Adult↗
PubMed1986

Expression of Ia antigen on retinal pigment epithelium in experimental autoimmune uveoretinitis.

Recently, human retinal pigment epithelial (RPE) cells have been demonstrated to express class II, HLA-DR, antigens both in vivo and in vitro. HLA-DR antigens were detected on RPE cells from patients with uveitis and retinitis pigmentosa. In addition, in vitro studies revealed that not only does this cell express HLA-DR antigen but also that this antigen can be modulated by the lymphokine, interferon (IFN)-gamma. In this study we evaluated the development of the murine class II, Ia, antigens on RPE cells in experimental autoimmune uveoretinitis (EAU). Ia antigen was evaluated with the avidin-biotin-peroxidase technique. Ia antigen was not detected on RPE cells from normal rats. However, Ia antigen was detected on the surface of RPE cells from EAU rats four days prior to the development of clinical and histopathological EAU. Moreover, the expression of Ia antigen on RPE cells from EAU rats continued to persist until one and one-half months after immunization. This study demonstrates that during the course of EAU the RPE cell is activated to express Ia antigens. This antigen expression may be important in the initiation and/or perpetuation of immune reactivity in the eye.

Animals↗
PubMed1985

Human T-cell leukemia/lymphoma virus I and/or Epstein-Barr virus-infected B-cell lines spontaneously produce acid-labile alpha-interferon.

B-cell lines were established as spontaneous outgrowths of cell cultures from patients with adult T-cell leukemia (ATL). Three such lines were shown to have integrated human T-cell leukemia/lymphoma virus 1 (HTLV-I) proviral sequences as well as Epstein-Barr virus (EBV) infection. Supernatant fluids from these cultured cells were assayed for interferon (IFN) production. Acid-stable alpha-IFN was found to be produced by one cell line (CF), and acid-labile alpha-IFN by the other two (HS, MJB). In contrast, HTLV-I-infected T-cell lines did not produce IFN. Some EBV-infected B-cell lines produce acid-labile alpha-IFN, while others do not. Since alpha-IFN, both acid stable and acid labile, is found in sera from patients with the polyclonal activation of B cells as a constitutive part of the disease, the above observations suggest a possible role of polyclonal B-cell activation in alpha-IFN production in these diseases.

B-Lymphocytes↗
PubMed1985

Class II antigen expression and gamma interferon modulation of monocytes and retinal pigment epithelial cells from patients with retinitis pigmentosa.

Monocytes from retinitis pigmentosa patients express diminished amounts of class II (HLA-DR) antigens in comparison to normal individuals, normal siblings of retinitis pigmentosa patients, glaucoma patients, and macular degeneration patients. This observation is correlated with a subnormal production of IFN-gamma, a potent regulator of class II antigen expression. When monocytes from retinitis pigmentosa patients are treated with IFN-gamma, the decreased expression of HLA-DR on the cell surface is restored to levels found on monocytes from normal individuals. HLA-DR antigens were detected on the surfaces of human retinal pigment epithelial cells grown in vitro and the expression of these antigens can be enhanced following IFN-gamma treatment. These data demonstrate an altered expression and regulation of class II, HLA-DR, antigens in a human eye disease. Since class II antigens and IFN-gamma are currently known to be necessary regulating proteins for efficient immune reactivity, these findings may indicate an immune disturbance in retinitis pigmentosa patients. Alternatively, this alteration may have nonimmune implications. For example, these studies may demonstrate an imbalance in systemic regulatory control systems and hence raise the possibility that these or related regulatory proteins and cell surface receptors may be instrumental in maintaining retinal integrity.

Cells, Cultured↗
PubMed1985

Histopathology of the subretinal fibrosis and uveitis syndrome.

A chorioretinal biopsy was obtained from a patient with subretinal fibrosis and chronic uveitis. The biopsy specimen was analyzed by conventional light and electron microscopy and by immunohistochemical methods. These demonstrated a markedly inflamed choroid with a predominance of B cells and plasma cells. Complement and IgG were deposited above Bruch's membrane. The subretinal fibrosis tissue contained islands of cells with retinal pigment epithelial characteristics; however, some of these cells demonstrated surface determinants of Müller cells. There were no circulating antiretinal antibodies detected nor could virus be cultured from the biopsy specimen. The clinical appearance of this entity is distinctive and consists of a chronic posterior uveitis with transient initial yellow-white deep retinal lesions and the later development of large white subretinal fibrotic areas. The EOG is markedly decreased. We hypothesize that the immunologic events involved in this entity include antibody production with immunoglobulin and complement deposition leading to retinal and retinal pigment epithelial destruction and a subretinal fibrous proliferation.

Adolescent↗