Biomedical subjects

R R Caspi

Publications and source records attributed to R R Caspi.

At least 73 records · Page 4Linked to original sources

PubMed1993

Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis.

Cell adhesion molecules are surface proteins important for cell migration and adhesion and are strongly expressed in eyes with inflammation. We studied the expression of two cell adhesion molecules: intercellular adhesion molecule-1 (ICAM-1, CD54) and lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) in mice with experimental autoimmune uveitis. B10.A mice were immunized with interphotoreceptor retinoid-binding protein and eyes were serially examined for expression of cell adhesion molecules using immunohistochemical staining. ICAM-1 was expressed on the vascular endothelium of the ciliary body and retina by 7 days after immunization, and LFA-1 was first expressed on some infiltrating inflammatory cells 9 days after immunization. Clear histologic evidence of ocular inflammation did not occur until 11 days after immunization. We then studied the effect of monoclonal antibodies against ICAM-1 and LFA-1 on the development of experimental autoimmune uveitis. Three groups of mice were immunized and treated for 21 days with daily intraperitoneal injections of rat monoclonal antibody against murine ICAM-1 or LFA-1 or with rat IgG as control. Ocular inflammation, graded clinically by examination of the fundus 14 and 21 days after immunization, was significantly decreased in animals treated with anti-ICAM-1 (P < 0.01 at Days 14 and 21) and with anti-LFA-1 antibody (P < 0.01 at Days 14 and 21). The intraocular inflammation graded histologically was also decreased in mice treated with anti-ICAM-1 and anti-LFA-1 antibody. This difference in the histologic grade of inflammation was statistically significant (P < 0.02) between mice treated with anti-ICAM-1 antibody and control mice and approached statistical significance (P < 0.10) in mice treated with anti-LFA-1 antibody compared to the control mice. Proliferative responses to lipopolysaccharide, PPD, and interphotoreceptor binding protein of lymphocytes obtained from the draining lymph nodes of mice treated with the antibodies were lower than those from the control mice, suggesting that cell-cell binding was impaired in treated mice. These data show that ICAM-1 is expressed in the eye before histologic evidence of inflammation, and that monoclonal antibodies against ICAM-1 and LFA-1 are effective in inhibiting experimental autoimmune uveitis in mice.

Animals↗

PubMed1993

Suppression of S-antigen-induced experimental autoimmune uveoretinitis in Lewis rats by oral administration with CGS-13080, a thromboxane synthetase inhibitor.

Oral administration of CGS-13080 [imidazo (1, 5-alpha) pyridine-5-hexanoic acid], a thromboxane synthetase inhibitor, has been reported to cause a marked reduction in serum thromboxane B2 concentration in humans and animals. Since thromboxane metabolites play an important role in ocular inflammation, the effect of oral CGS-13080 in the development of experimental autoimmune uveoretinitis in Lewis rats has been investigated. Females were immunized with bovine S-antigen (S-Ag). Treatment was started on day 0 of immunization. Animals were divided into three groups. The control group was fed a standard pellet diet, while the treated groups were fed the standard diet supplemented with either a low dose (0.8 g per 10 kg pellet) or a high dose (1.6 g per 10 kg pellet) of CGS 13080. From day 10 after immunization, the eyes of these rats were examined daily for clinical evidence of experimental autoimmune uveoretinitis. On day 14, the eyes were collected for histologic study. The cellular immune responses were evaluated on the draining inguinal lymph nodes. Blood samples were also collected for the measurement of anti-S-Ag antibody production, thromboxane B2 and prostaglandin A2 levels. Clinical disease developed in 73.3% of the control rat group, 30.0% of the low-dose treated group and 17.6% of the high-dose group. The average histologic grade was 1.9 in the control group, 0.65 in low-dose group and 0.32 in high-dose group. Lymphocyte proliferation to S-Ag paralleled the clinical disease scores. Average stimulation indices were 10.9 in the controls, 7.5 in the low-dose group and 2.2 in the high-dose group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Recruitment of antigen-nonspecific cells plays a pivotal role in the pathogenesis of a T cell-mediated organ-specific autoimmune disease, experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) is a prototypic T cell-mediated autoimmune disease, whose target tissue is the neural retina, that is used as a model for a number of human blinding ocular diseases of a presumed autoimmune nature. EAU in rats can be induced by adoptive transfer of small numbers of retinal antigen-specific CD4+ T cell lines. Although recruitment mechanisms were assumed to play a role in the immunopathogenesis of uveitis, there is no direct evidence that would permit assessment of the importance of recruited non-antigen-specific T cells in retinal autoimmunity. In the present study, we addressed this question by using congenitally athymic Lewis rats (LEW.rnu/rnu), that are deficient in functional endogenous T cells, but are otherwise syngeneic with the euthymic Lewis rats that develop characteristically severe EAU. The uveitogenic stimulus was delivered in the form of phenotypically and functionally homogeneous pathogenic T cell lines, specific to the major pathogenic epitope of either the intracellular photoreceptor protein, S-Ag, or the extracellular photoreceptor matrix protein, IRBP. Depending on the T cell line used, EAU in athymic rats was either drastically reduced in severity (IRBP), or essentially absent (S-Ag). Susceptibility was restored when the athymic animals were reconstituted with immunocompetent T cells from syngeneic euthymic donors. While the intraocular infiltrate in euthymic rats was predominantly lymphocytic, with smaller numbers of monocyte/macrophages and even fewer neutrophils, the sparse infiltrate in athymics was largely monocytic, and with a relatively high proportion of neutrophils and eosinophils. Reconstituted animals had an intermediate histological picture with respect to the infiltrating cell types and disease severity. Our data are consistent with the interpretation that recruitment of naive T cells constitutes an amplification mechanism that is central to the expression and pathogenesis of uveitis. The extent of dependence on this phenomenon appears to be influenced by the antigenic specificity of the T cell line, and could be connected to the 'accessibility' of the target antigen in vivo.

Animals↗

PubMed1992

Analysis of an in vitro-generated signal that induces systemic immune deviation similar to that elicited by antigen injected into the anterior chamber of the eye.

The selective deficit in delayed hypersensitivity that characterizes anterior chamber-associated immune deviation (ACAID) is the direct result of a blood borne, Ag-specific, cell-associated signal that is created after Ag is injected into the anterior chamber of the eye of normal mice. The cells that carry this signal via the blood to the spleen express the mature macrophage marker F4/80 and are similar to, or perhaps even arise from, F4/80+ dendritic cells found within the stroma of normal iris and ciliary body. We have recently reported that ACAID-inducing properties can be conferred upon conventional F4/80-bearing macrophages harvested from the normal peritoneal cavity by incubating these cells in vitro with the soluble protein Ag, BSA, in the presence of supernatants harvested from cultured iris and ciliary body cells. Using this in vitro induction system, we have examined the limiting conditions for conferring ACAID-inducing potential on peritoneal exudate cells. We have found that an ACAID-inducing signal can be created in vitro with several different soluble Ag, including the retinal autoantigen-interphotoreceptor retinol binding protein, and that active endocytosis and processing by peritoneal exudate cells is required because chloroquine prevents these cells from acquiring ACAID-inducing properties. In addition, we have determined that for supernatant-treated peritoneal macrophages to induce ACAID to soluble Ag the cells must be 1) alive, 2) injected i.v. or i.p. (but not s.c.), and 3) administered to recipients with an anatomically intact spleen. When these conditions are met, as few as 20 F4/80+ macrophages pulsed with Ag in the presence of iris and ciliary body supernatants are sufficient to induce ACAID. Macrophage hybridomas derived from "conventional" APC can acquire ACAID-inducing potential in vitro if exposed to iris and ciliary body supernatants, whereas macrophage hybridomas derived from "suppressor inducer" APC constitutively possess ACAID-induced potential. Peritoneal macrophages that were endowed with ACAID-inducing properties by in vitro exposure to supernatants were found to elicit splenic suppressor cells similar to those found in spleens of mice with ACAID. Moreover, the expression of experimental autoimmune uveitis in mice immunized with interphotoreceptor retinol binding protein was significantly suppressed if the animals were pretreated with peritoneal exudate cells pulsed with this Ag in the presence of iris and ciliary body supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Genetic control of susceptibility to experimental autoimmune uveoretinitis in the mouse model. Concomitant regulation by MHC and non-MHC genes.

Experimental autoimmune uveoretinitis (EAU) in animals is a T cell-mediated autoimmune response directed against cells of the neural retina, in particular the photoreceptors. EAU can be induced in susceptible strains of mice by immunization with purified retinal Ag, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of MHC vs non-MHC genes in the control of susceptibility to ocular autoimmunity using the mouse EAU model. Selected strains representing most of the known independent H-2 haplotypes, as well as several H-2-recombinant and congenic strains, were immunized with interphotoreceptor retinoid-binding protein. Ocular pathology was induced in strains of the H-2k haplotype and their I-A-matched congenics, as well as in strains of the H-2r, H-2b, and H-2d haplotypes. In a series of experiments utilizing intra-H-2 recombinant strains, MHC control of susceptibility was tentatively mapped to the I-A subregion of the H-2k. Expression of the I-Ek gene product was not required for susceptibility to EAU, and in fact appeared to have an ameliorating effect on disease. Incidence and severity of disease obtained in strains sharing the same H-2 on a different background, or sharing the same background in the context of a different H-2, indicated that non-MHC genes contribute significantly to the regulation of EAU. Disease expression of susceptible H-2 haplotypes was highest in strains with B10 background (permissive) and ranged from intermediate to absent in strains with other (nonpermissive) backgrounds. The data suggest that although the ability to develop ocular pathology is dependent on the I-A subregion of the H-2, the final expression of disease in susceptible haplotypes is largely determined by background, non-MHC genes.

Animals↗

PubMed1992

Suppression of experimental autoimmune uveitis in mice by induction of anterior chamber-associated immune deviation with interphotoreceptor retinoid-binding protein.

Immunization with bovine interphotoreceptor retinoid-binding protein induces autoimmune uveitis in B10.A mice. We have examined whether this soluble retina-specific Ag can induce anterior chamber-associated immune deviation when injected into the anterior chamber (AC) of the eye, and whether this deviant immune response has any effect on uveitis is susceptible mice. The results of these experiments indicate that interphotoreceptor retinoid-binding protein (IRBP) injected intracamerally altered the subsequent immune response of B10.A mice such that a) they were not able to develop IRBP-specific delayed hypersensitivity, nor (b) were they able to express significant autoimmune uveitis following a uveitogenic regimen. Moreover, spleen cells from mice that received IRBP in the AC suppressed uveitis when adoptively transferred into naive recipients. The splenic suppressor cells were able to prevent autoimmune uveitis in recipient mice when administered after the uveitogenic regimen. Most important, IRBP-specific splenic cells from mice treated with IRBP in the AC when injected into mice with established uveitis caused an abrupt cessation of the intraocular inflammation. The ability of intracamerally-injected soluble Ag to induce suppressor T cells that act on the efferent limb of the immune response suggests that the anterior-chamber-associated immune deviation phenomenon may have physiologic relevance in terms of preservation of the integrity of ocular tissue and renders this approach particularly suitable for treating already established experimental autoimmune diseases of this type. These results are discussed in terms of other methods that have been devised experimentally to suppress and prevent autoimmune uveitis and encephalomyelitis.

Animals↗

PubMed1992

Control of experimental autoimmune uveoretinitis by low dose T cell vaccination.

Autoimmune T lymphocytes can be used under appropriate conditions to induce resistance to the specific autoimmune disease that they usually produce. This practice, termed T cell vaccination, was found to be effective with the injection of a low (subpathogenic) number of autoaggressive T line lymphocytes. We report here that T cell vaccination produced marked resistance to the expression of experimental autoimmune uveoretinitis (EAU) in Lewis rats. In addition, vaccination led to the appearance of lymphoid cells in the vaccinated rats that demonstrated proliferative responses against idiotypic and ergotypic specificities of the injected T cells. This is the first report demonstrating the effector T lymphocytes specific for ocular antigens may be used as agents to modulate immunopathogenic responses responsible for EAU.

Amino Acid Sequence↗

PubMed1992

Association between mast cells and the development of experimental autoimmune uveitis in different rat strains.

To study the role of anterior uveal mast cells in experimental autoimmune uveitis (EAU), the mast cells in the iris and ciliary body of Lewis rats, Brown Norway (BN) rats, and their F1 hybrids (LBNF1) were quantitated in normal rats and during the induction period of EAU. The mean baseline mast cell number was 68.9 +/- 10.8 per anterior uvea for Lewis rats, 0.3 +/- 0.2 for BN rats, and 4.6 +/- 0.6 for LBNF1 rats. Detectable mast cells in the anterior uvea of S-Ag-immunized Lewis rats decreased to 60% of control at 6 days postimmunization, recovered to 80% at 10 days, and dropped again to 16% at 13 days, with disease onset around 14 days. In Lewis rats that were adoptively transferred with a uveitogenic T-lymphocyte line, a profound drop in anterior uveal mast cell numbers occurred in the eyes with early signs of EAU, 3 days after the transfer. The decrease in detectable mast cells is consistent with mast cell degranulation. The data suggest that anterior mast cells participate in the immunopathogenesis of EAU and may influence the genetic susceptibility to EAU.

Animals↗

PubMed1992

Predominant usage of V beta 8.3 T cell receptor in a T cell line that induces experimental autoimmune uveoretinitis (EAU).

Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease induced in animals by immunization with retinal proteins (or synthetic fragments derived from them) in adjuvant, and it is considered a model of human autoimmune diseases of the eye. To study the T cell clonotypes that may be involved in EAU, we analyzed the T cell repertoire of three related T cell lines: the pathogenic line LR16, specific to the major uveitogenic epitope of IRBP; its pathogenic subline J; and its nonpathogenic subline A. We examined the expression of the genes coding for the variable regions of the 20 known Lewis rat T cell antigen receptor (TCR) V beta families. The nonpathogenic subline was found to contain mostly T cells expressing V beta 5, V beta 8.2, and V beta 19 while the pathogenic subline consisted mainly of cells expressing V beta 8.3 TCRs. Genomic Southern blot analysis of DNA from the pathogenic subline showed that V beta 8.3-expressing T cells were the dominant clonotype, and DNA sequence analyses of V beta 8.3 cDNAs revealed that two V beta 8.3 TCRs were expressed in the pathogenic subline. One of the V beta 8.3 cDNAs encoded a variable region gene segment identical to previously reported rat V beta 8.3 TCR while the other differed by two amino acids in the second complementarity determining region (CDR2). Taken together with previous data showing overrepresentation of V beta 8-expression in T cell lines that induce EAU, but not in nonuveitogenic T cell lines, our results suggest that V beta 8.3-expressing T cells represent a pathogenic clonotype in IRBP-induced EAU.

Amino Acid Sequence↗

PubMed1992

Genetic factors in susceptibility and resistance to experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) can be induced in susceptible stains of rats and mice by immunization with purified retinal antigens, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of major histocompatibility complex (MHC) vs. non-MHC genes in the control of susceptibility to ocular autoimmunity, using the mouse and the rat EAU models. It was shown that EAU expression in mice requires both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility was tentatively mapped to the I-A subregion in H-2k. I-Ek expression appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include diverse genetic mechanisms spanning regulation of cytokines, hormones, vascular effects and the T cell repertoire. Taken together, the data suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background.

Animals↗

PubMed1992

Use of ACAID to suppress interphotoreceptor retinoid binding protein-induced experimental autoimmune uveitis.

Experimental Autoimmune Uveitis (EAU) was induced by immunization with bovine interphotoreceptor retinoid binding protein (IRBP) in B10.A mice. The experiments were performed to evaluate whether Anterior Chamber Associated Immune Deviation (ACAID) can be induced by IRBP when injected intracamerally. The results indicate that anterior chamber (AC) injection of IRBP impaired the development of IRBP-specific delayed hypersensitivity and prevented the expression of EAU following immunization with IRBP-CFA. Adoptive transfer of spleen cells obtained from mice that received IRBP into AC suppressed EAU, whether administered prior to or after the uveitogenic regimen. Most important, IRBP-specific suppressor cells from AC-IRBP treated mice when injected into IRBP-EAU mice suppressed and eliminated already established intraocular inflammation. IRBP-specific, ACAID-inducing suppressor T cells act on the efferent limb of the immune response, and represent ideal modalities for treating already established EAU.

Animals↗

PubMed1991

Combined anti-interleukin-2 receptor and low-dose cyclosporine therapy in experimental autoimmune uveoretinitis.

The effect of combination treatment with anti-interleukin-2 (IL-2)-receptor monoclonal antibody (ART18) and cyclosporine A (CsA) on the effector stage of experimental autoimmune uveoretinitis (EAU) was examined. Efferent-stage EAU was induced in Lewis rats by adoptive transfer of a T-helper cell line specific to retinal soluble antigen (SAg). Rats were treated with ART18 (0.5 mg/kg/day), low dose CsA (1.5 mg/kg/day), or a combination of both. The results were compared to groups treated with high dose CsA (10 mg/kg/day) and to sham-treated animals, with respect to clinical and histological EAU, lymphocyte proliferative responses to SAg, and the ability to transfer EAU to secondary recipients. Ten-day combination therapy with ART18 and low-dose CsA was more effective than high-dose CsA and almost completely suppressed EAU development. ART18 as sole therapy was partially effective, and was better than low dose CsA as sole therapy. Splenocytes of protected animals did not transfer EAU to secondary recipients, while splenocytes of sham-treated controls did, suggesting that the number of uveitogenic lymphocytes in the treated host was reduced by the therapy. In contrast, this therapy was completely ineffective against EAU induced by active immunization. The possible reasons for this discrepancy between the two respective models of EAU are discussed.

Animals↗

PubMed1991

Inhibition of T lymphocyte proliferation by retinal glial Müller cells: reversal of inhibition by glucocorticoids.

Study of interactions between retinal glial Müller cells and T lymphocytes have revealed a wide array of reciprocal influences on the functions of these cells. In the present study we show that these interactions can be further modified by corticosteroid hormones. The primary effect of Müller cells on T lymphocytes is an inhibition of the T-cell proliferative response, and it is exerted via a membrane-bound factor. In this report we show that glucocorticoids can reverse the inhibition by suppressing the expression of the Müller cell inhibitory factor. This effect was independent of the action of glucocorticoids on arachidonic acid metabolism.

Animals↗

PubMed1991

T cell receptor beta-chain usage in experimental autoimmune uveoretinitis.

Genomic rearrangements to the T-cell receptor (TCR) V beta 8 gene locus were examined in T cells derived from the lymph nodes of Lewis rats immunized with either S-Antigen or peptides derived from interphotoreceptor retinoid binding protein (IRBP). The cells used in these studies are from T-cell lines that have been selected by several cycles of antigen/IL-2 stimulations, or clones isolated from these lines. No apparent rearrangement of the V beta 8 gene was observed by Southern analysis, suggesting that if indeed there are T cells using V beta 8 gene elements they represent small proportions of the cells in these T-cell lines that induce EAU (uveitogenic T cells) and that the lines may consist of large numbers of clones. On the other hand, we have demonstrated V beta 8 gene expression in uveitogenic T-cell populations by Northern analysis and by polymerase chain reaction (PCR). Although V beta 8 gene transcripts were detectable in pathogenic, but not in non-pathogenic, T-cell lines using a V beta 8 cDNA probe, RNA from pathogenic T cell lines did not hybridize to another probe specific for rat V beta 8.2. Taken together, these results suggest that, unlike the T-cell lines that mediate experimental allergic encephalomyelitis (EAE), some T-cell lines that induce EAU do not predominantly express V beta 8.2 gene but other member(s) of the V beta 8 family.

Animals↗

PubMed1991

[Active immune regulation by cells of the ciliary body].

Immunoregulation in the eye requires both an effective defense against exogenous pathogens and protection of the delicate anatomy of the eye against "innocent bystander destruction", which accompanies inflammatory reactions. We studied the role of uveal cells for local immunoregulation in the eye and investigated the effect of cultured Lewis rat ciliary body cells on antigen-specific 3[H]-thymidin incorporation in a T-helper-lymphocyte cell line (ThS) specific for the retinal-soluble antigen (SAg). Ciliary body cells inhibit the proliferation of ThS. This inhibition is not species-specific and is mediated by at least two mechanisms: a soluble inhibitor and a contact-requiring factor that is trypsin-sensitive, suggesting a protein molecule. After removal of these inhibitory components, ciliary body cells also exhibit the capacity to effectively present SAg to ThS. This dual effect of ciliary body cells on T-helper lymphocytes supports the concept of active local immunoregulation in the eye.

Animals↗

PubMed1991

[Immunologic suppression of experimental autoimmune uveitis].

Experimental autoimmune uveitis (EAU) is induced in rats by active immunization with retinal S-Antigen (S-Ag) in complete Freund's adjuvant. In contrast, oral administration of an antigen induces specific suppression. We investigated the potential of oral administration of S-Ag for the treatment of EAU. Prior to active immunization rats received 3 x 1 mg S-Ag orally. In contrast to untreated controls, the treated rats were significantly protected from EAU, as determined by clinical and histological examination. Lymphocytes from treated rats showed no proliferative response to S-Ag in vitro, but had a normal proliferative response to other antigens. CD8-positive T cells from S-Ag-fed rats inhibited the proliferation of an antigen-specific uveitogenic T-cell line in vitro. Moreover, the intensity of the inflammatory reaction to active immunization could be suppressed when feeding was started after the active immunization. These data show, that oral administration induced suppression, which provided significant protection from the development of uveitis.

Administration, Oral↗

PubMed1990

Inhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen.

The ability to prevent the expression of retinal SAg induced experimental autoimmune uveitis (EAU) in Lewis rats by oral administration of the SAg and SAg fragments was investigated. Oral administration of the SAg molecule prevented or markedly diminished the clinical appearance of SAg-induced disease as measured by ocular inflammation. Furthermore, oral administration of the SAg also markedly diminished uveitis induced by the uveitogenic M and N fragments of the SAg. M and N fragments were not effective in preventing SAg-induced EAU, although feeding the M fragment prevented disease induced by the M fragment. Oral administration of the SAg did not prevent myelin basic protein induced experimental autoimmune encephalomyelitis, whereas feeding myelin basic protein did. In vitro studies demonstrated a significant decrease in proliferative responses to the SAg in lymph node cells draining the site of immunization from fed vs nonfed animals. Furthermore, the addition of splenocytes from SAg-fed animals to cultures of a CD4+ SAg-specific cell line profoundly suppressed the cell line's response to the SAg, whereas these splenocytes had no effect on a purified protein derivative-specific cell line. The Ag-specific in vitro suppression was blocked by anti-CD8 antibody (OX-8) demonstrating that this suppression is dependent on CD8+ T-cells. These experiments demonstrate that Ag-specific immunomanipulation can be achieved in the EAU model by oral administration of the SAg and raise the possibility that such an approach may have practical clinical implications in uveitis as well as other human autoimmune diseases.

Administration, Oral↗

PubMed1990

Dual effect of ciliary body cells on T lymphocyte proliferation.

The interaction between organ-resident cells from the anterior uvea of the eye and T helper (Th) cells was investigated. Cells from Lewis rat ciliary body processes (CB cells), grown in tissue culture using an explant technique, could be induced to express major histocompatibility complex class II (Ia) antigens by incubation with rat interferon-gamma. Ia+ CB cells only poorly functioned as antigen-presenting cells (APC) for a syngeneic, uveitogenic Th cell line specific for the retinal soluble antigen (SAg). Moreover, if added to an Ag-driven lymphocyte proliferation assay in the presence of conventional APC, the rat CB cells had an inhibiting effect on Th proliferation. This inhibitory activity was not species specific, since similar effects were observed with bovine and human ciliary epithelial cells. The suppressive activity of CB cells was composed of a soluble factor, as well as a membrane-associated inhibitor. The soluble activity did not appear to be related to transforming growth factor-beta (TGF-beta), since no reversal of inhibition by a neutralizing antibody to TGF-beta was found. Part of the soluble inhibitory activity could be reversed by indomethacin treatment. The membrane-associated component was trypsin sensitive, suggesting a protein molecule. After abrogation of the inhibitory capacity by trypsin treatment and fixation by glutaraldehyde, CB cells effectively presented SAg to Th cells. These data suggest that CB cells are capable of mediating both Ag presentation and inhibition of Th cell proliferation.

Animals↗