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PubMed1992

Antigen presenting capacity of human decidua: no evidence for human decidual antigen presenting cell mediated immunoregulation.

Decidual antigen presenting cell (APC) mediated maternal immunoregulation has been reported. In the present study the ability of villous chorion as well as fetal cell pulsed early human pregnancy decidual APC to generate selectively antigen non-specific and MHC class II unrestricted CD8 positive T suppressor cells was reassessed in view of the fact that placental trophoblast, unlike the fetus, constitutes the fetal tissue of major contact at the maternal-fetal interface. Neither fetal cell nor villous chorion pulsed decidual APC generated maternal T cells with the ability to immunosuppress PHA-, Con A- and PWM-induced autologous or allogeneic lymphoproliferation. In only 2 out of 45 assays with villous chorion pulsed decidual APC was significant inhibition of mitogen induced lymphoproliferation detected and on no occasion with fetal cell pulsed decidual APC. No change in CD4/CD8 ratio of the maternal putative regulatory cells was detected by FACS analysis compared with control cultures. These findings suggest that decidual APC mediated immunoregulation plays no role in directing the maternal immune response.

Antigen-Presenting Cells↗

PubMed1992

Antigen presentation by murine splenic, but not hepatic, antigen-presenting cells to induce IL-2/IL-4 production from immune T cells is regulated by interactions between LFA-1/ICAM-1.

Pretransplant transfusion of multiple minor histoincompatible spleen cells to naive recipient mice by the portal vein suppresses the ability of those animals to reject skin grafts from mice syngeneic with those used for transfusion, and decreases in vitro immunity on rechallenge with the same antigens, by comparison with mice receiving transfusion by the lateral tail vein. We have shown elsewhere that this is correlated with a diminished activation of Th1 cells for IL-2 production, without apparently affecting activation of Th2 cells for IL-4 production. Similar data are obtained by merely infusing hepatic (vs. splenic) antigen-presenting cells (APC) into normal mice, or by challenging immune cells in vitro with antigen-pulsed hepatic (vs. splenic) APC. However, when antigen-pulsed splenic APC are incubated with immune T cells in the presence of anti-LFA-1 monoclonal antibody (Mab), selective activation of Th2 cells (as is seen with hepatic APC) again occurs at the expense of activation of Th1 cells. Anti-LFA-1 Mab causes little perturbation in lymphokine production from T cells stimulated with hepatic APC. Using cDNA probes for IL-2 and IL-4 we show that T-cell activation in the presence of anti-LFA-1 Mab leads to selective inhibition of transcription of IL-2 mRNA.

Animals↗

PubMed1992

Targeting antigens to antigen presenting cells.

Antigen may be targeted to antigen presenting cells (APC) by conjugating the antigen to monoclonal antibodies directed against surface molecules on APC. By now several laboratories have shown that immunotargeting enhances humoral responses, depending upon the targeted ligand or cell type, with low doses of antigen and without the use of adjuvants. There is also preliminary evidence that the method may be used to bias immune responses in desired directions, possibly also to induce tolerance. In addition to its use as an experimental tool for exploring immune reactions the method could in the future also be clinically important, e.g. in vaccination. In this article we give a brief account on work so far published with this novel method and discuss possible mechanisms behind its immunopotentiating effects.

Animals↗

PubMed2002

Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance.

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4-48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of alphaDEC-205:OVA to DCs in the steady state initially induced 4-7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with alphaDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic alphaCD40 antibody produced large amounts of interleukin 2 and interferon gamma, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.

Animals↗

PubMed1986

Antigen presentation by hapten-specific B lymphocytes. III. Analysis of the immunoglobulin-dependent pathway of antigen presentation to interleukin 1-dependent T lymphocytes.

The ability of antigen-specific murine B lymphocytes to present antigen to a normal (nontransformed) antigen-specific, interleukin (IL)1-dependent T cell clone and to heterogeneous T lymphocytes was investigated. Hapten-specific lymphocytes present protein antigens to both the D10G.4.1 T cell clone and heterogeneous immune T cells. When the antigen bears an epitope recognized by the specific B cell, the subsequent presentation of this antigen is 10(2)-10(4)-fold more efficient, as compared to the same, but nonhaptenated protein. The requisite B lymphocyte binds hapten, is radiosensitive and is nonadherent to plastic. The hapten-specific antigen presentation is blocked by antibodies to the surface Ig receptor, while the presentation of unmodified protein is unaffected. These observations are identical to our findings in studies of B cell antigen presentation to T-T hybridomas and therefore demonstrate the generality of the immunoglobulin-dependent pathway of presentation. However, in contrast to the results with T-T hybridomas, the specific B lymphocytes are necessary, but not sufficient, to activate IL 1-dependent T cells. A third cell is required for both B lymphocyte immunoglobulin-dependent and nonspecific antigen-presentation. This cell is radioresistant, plastic adherent and of low density. The requirement for this third cell can be circumvented by supplementing cultures with highly purified IL 1. These results demonstrate that the remarkably efficient ability of B lymphocytes to present antigen is operative with factor-dependent T lymphocytes. Furthermore, conventional accessory cells also appear to play a role in this process, which is consistant with their known requirement in antigen-specific T-B interactions in the generation of antibody responses.

Animals↗

PubMed1997

Exogenously provided peptides fail to complex with intracellular class II molecules for presentation by antigen-presenting cells.

Exogenously supplied antigenic peptides can bind to and be presented by cell surface class II molecules of APCs without prior processing. However, it has been unclear whether peptide Ags exogenously supplied to APCs can also form complexes with nascent intracellular class II molecules that contribute to Ag presentation. We found that exogenously provided peptide Ags, unlike whole protein Ags, are presented as efficiently by fixed as by unfixed B lymphoblastoid APCs, suggesting that intracellular processes do not contribute to the presentation of exogenously supplied peptides by unfixed APCs. Consistent with this finding, exogenously provided peptides do not bind detectably to nascent intracellular class II molecules. We studied the basis for this failure. First, as compared with whole proteins, exogenously supplied peptides accumulate very poorly intracellularly. Second, peptides are more rapidly exocytosed. The limited ability of APCs to accumulate exogenously supplied peptides intracellularly provides a likely explanation for the failure of these peptides to associate with nascent intracellular class II molecules. Exogenously supplied peptides probably never reach the intracellular vesicles in which peptide loading of class II molecules occurs. These findings have implications for the use of peptides therapeutically to block presentation of autoantigens in autoimmune disease.

Antigen Presentation↗

PubMed1989

Antigen presentation by neonatal murine spleen cells.

The ability of murine neonatal spleen cells to present soluble antigen to T-helper cells and to produce growth factors in response to subsequent cellular interactions was studied. The T-helper-cell line (D10-G4.1) (D10), which is specific for the soluble antigen conalbumin presented on H-2-matched (H-2k) antigen-presenting cells, was used as cooperating and indicator cells in these cellular interactions. The D10 cells are TH2 T-helper cells which secrete the autocrine growth factor IL-4 and can also respond to exogenous IL-2 (T. R. Mosmann and R. L. Coffmann, Immunol. Today 8, 223, 1987). D10 cells require exogenous IL-1 for their proliferation and secrete, in addition to IL-4, IL-1 inducer factor and GM-CSF. The ability of neonatal spleen cells to present antigen and to stimulate D10 cells to produce IL-4 and proliferate is low. During antigen presentation there is an augmentation of IL-1 and IL-2 production by the antigen-presenting spleen cell population. However, neonatal spleen cells do not respond to the same levels as do adult spleen cells. The addition of exogenous IL-1 cannot repair the antigen presentation by neonatal cells. Experiments in which the antigen processing and presentation steps were separated from those requiring growth factor induction and secretion demonstrate that neonatal spleen cells are impaired in their ability to perform adequate antigen processing and presentation. The neonatal spleen cells are as competent as adult cells to cooperate with T-helper cells and secrete growth factors, provided antigen processing and presentation is performed by fully competent adult spleen cells. Experiments in which neonatal and adult antigen-presenting spleen cell populations were mixed, and others in which plastic adherent and nonadherent cells were separated, could not detect any suppressor mechanisms responsible for the low antigen presentation of neonatal cells. Thus, neonatal spleen cells are impaired in the initial stages of antigen processing and presentation. This impairment which leads to low levels of growth factor production is the major determinant in the ineffectual stimulation of T-helper cells by neonatal spleen cells.

Animals↗

PubMed1988

Regulation of antigen-presentation-I. IFN-gamma induces antigen-presenting properties on B cells.

B cells require activation to efficiently present Ag to T cells. In agreement with this earlier observation we show that live, mitomycin C-treated B cells, but not B cells fixed in paraformaldehyde, stimulated the growth of allogeneic T cells in the primary MLR. However, if B cells were cultured with anti-Ig antibodies and IFN-gamma before fixation they acquired excellent T cell stimulatory activity. Neither reagent alone conferred this novel co-stimulatory function on the B cell surface. The activity induced by both stimuli was not attributed to an increase expression of class II-MHC molecules or IL-1. IL-2 or IL-4, in combination with anti-Ig, also induced B cell stimulatory activity, but were less effective than IFN-gamma. TNF failed to stimulate B cells, but synergized with IFN-gamma in the induction of this activity. These studies therefore demonstrate an important role for lymphokines in modulating B cell Ag-presenting activity as well as the acquisition by B cells of a novel co-stimulatory surface activity.

Animals↗

PubMed2006

Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules.

Dietary supplementation with polyunsaturated fatty acids (PUFAs) has immunosuppressive effects; however, the molecular targets of PUFAs and their mode of action remain unclear. One possible target is antigen presentation to T cells through the human leukocyte antigen (HLA) class I pathway. Here we show that incorporation of PUFAs lowers target cell susceptibility to lysis by effector T cells. Treatment of B lymphoblast targets with the omega-6 PUFA arachidonic acid (AA) or omega-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by approximately 20-25%. HLA class I surface levels and their rate of endoplasmic reticulum (ER)-Golgi traffic were also reduced by PUFA treatment. Calibration experiments showed that the approximately 15% reduction in surface HLA I was not sufficient to completely account for the decreased lysis. However, PUFAs significantly lowered antigen-presenting cell-T cell conjugate formation, by approximately 30-40%. Taken together, our data show for the first time that an omega-6 and an omega-3 PUFA affect the HLA class I pathway of B lymphoblasts. Our findings suggest that elimination of self- and pathogen-derived peptides by effectors may be compromised by dietary PUFA supplementation. In addition, PUFA-mediated changes in ER-Golgi trafficking point to a new area of PUFA modulation of immune responses.

Antigen-Presenting Cells↗

PubMed1990

Parasite-accessory cell interactions in theileriosis. Antigen presentation by Theileria annulata-infected macrophages and production of continuously growing antigen-presenting cell lines.

Theileria annulata, a protozoan parasite of cattle, infects major histocompatibility complex (MHC) class II+ cells, particularly macrophages, and transforms them into continuously growing cell lines. We examined the effects of parasitism by T. annulata on antigen-presenting cell function. T. annulata-infected cells (TaH) presented ovalbumin (as measured by [3H]thymidine incorporation) to both resting autologous bovine T cells and ovalbumin-specific bovine CD4+ T cell lines. However, the former cells were also stimulated by TaH without exogenous antigen although to a lesser degree than in the presence of antigen. This "nonspecific" proliferation was not seen with the ovalbumin-specific T cell lines. The magnitude of response by resting T cells in the presence of antigen, to TaH or purified peripheral blood monocytes, was essentially similar. However, on a per cell basis fewer TaH were required. Considerably greater proliferation to antigen was seen with the ovalbumin-specific T cell lines in the presence of TaH compared to monocytes and again fewer TaH were required to elicit a response. The kinetics of processing did not appear to be substantially altered in TaH and the increased proliferation may be due to the elevated MHC class II expression of these cells. Genetic restriction studies with the T cell lines indicated that the restricting elements used to present ovalbumin by TaH were the same as those used by monocytes, as identified by an isoelectric focusing technique. The continuously growing cell lines provide us with a unique model for investigating parasite-accessory cell interactions in theileriosis. The augmented antigen presenting cell activity of TaH may play an important role in the pathogenesis of the disease. TaH will also provide us with a valuable resource for our antigen presentation studies. In particular, the enhanced antigen presentation by TaH enabled us to detect responses to lower levels of antigen, often an important consideration for experiments where the quantity of antigen available is the major limiting factor.

Animals↗

PubMed2001

Toxoplasma gondii and MHC-restricted antigen presentation: on degradation, transport and modulation.

Resistance against Toxoplasma gondii, an obligate intracellular protozoan parasite surrounded by a parasitophorous vacuolar membrane, is mediated by the cellular arm of the immune system, namely CD8+ and CD4+ T cells. Thus, priming and activation of these cells by presentation of antigenic peptides in the context of major histocompatibility complex class I and class II molecules have to take place. This is despite the fact that the vacuolar membrane avoids fusion with the endocytic compartment and acts like a molecular sieve, restricting passive diffusion of larger molecules. This raises several cell biological and immunological questions which will be discussed in this review in the context of our current knowledge about major histocompatibility complex-restricted antigen presentation in other systems: (1) By which pathways are parasite-derived antigens presented to T cells? (2) Has the parasite evolved mechanisms to interfere with major histocompatibility complex-restricted antigen presentation in order to avoid immune recognition? (3) To what extent and by which mechanism is antigenic material, originating from the parasite, able to pass through the vacuolar membrane into the cytosol of the infected cell and is it then accessible to the antigen presentation machinery of the infected cell? (4) What are the actual antigen-presenting cells which prime specific T cells in lymphoid organs? An understanding of these mechanisms will not only provide new insights into the pathogenesis of Toxoplasma gondii and possibly other intravacuolar parasites, but will also improve vaccination strategies.

Animals↗

PubMed2000

Activation of alloreactive T cells by allogeneic nonprofessional antigen-presenting cells and interleukin-12 from bystander autologous professional antigen-presenting cells.

BACKGROUND: After solid organ transplantation most alloantigens are presented to the recipient's immune system by normal tissue cells, which can be considered to act as nonprofessional antigen-presenting cells (APC). It is well accepted that such nonprofessional APC fail to activate recipient resting T cells due to their inability to deliver costimulatory activity. In our study, we tested a hypothesis that such costimulatory activity may be provided by "bystander" recipient professional APC. METHODS: We set up mixed lymphocyte cultures (MLC) of purified T cell responders and T cell stimulator cells, the latter as nonprofessional APC carrying allogeneic MHC class I and II, and tested if responder-type autologous APC could facilitate responder T cell proliferation. In this assay also the effects of anti-CD28 antibody and interleukin- (IL) 1beta, IL-6, or IL-12 mediated costimulation on responder T cell proliferation and IL-2 production were investigated. RESULTS: Autologous APC, i.e., monocytes, were found to facilitate the proliferative response of resting T cells stimulated by allogeneic nonprofessional APC. IL-12 was identified as the most important costimulatory factor for induction of proliferation. IL-1beta enhanced IL-2 production and proliferation of allostimulated resting T cells but its presence was not essential. Although CD28 triggering alone was ineffective, this costimulatory pathway enhanced IL-2 production and proliferation when combined with IL-12 or IL-1beta. CONCLUSIONS: We conclude that costimulatory activity for activation of resting human T cells by nonprofessional donor APC can be delivered through activity of bystander recipient-type autologous APC. This mechanism of allostimulation may contribute to the induction and perpetuation of alloreactivity "in vivo" in a time frame when intragraft professional donor-type APC have been replaced with professional recipient-type APC.

Antibodies↗

PubMed2005

Apolipoprotein-mediated pathways of lipid antigen presentation.

Peptide antigens are presented to T cells by major histocompatibility complex (MHC) molecules, with endogenous peptides presented by MHC class I and exogenous peptides presented by MHC class II. In contrast to the MHC system, CD1 molecules bind lipid antigens that are presented at the antigen-presenting cell (APC) surface to lipid antigen-reactive T cells. Because CD1 molecules survey endocytic compartments, it is self-evident that they encounter antigens from extracellular sources. However, the mechanisms of exogenous lipid antigen delivery to CD1-antigen-loading compartments are not known. Serum apolipoproteins are mediators of extracellular lipid transport for metabolic needs. Here we define the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in APCs. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by APCs as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander APCs. Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens.

Animals↗

PubMed1983

Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity.

Immune responses are initiated by HLA-DR+ cells, which present antigen to T cells. Observations that HLA-DR may be experimentally induced on thyroid epithelium and that HLA-DR occurs on thyrocytes in autoimmune thyroid diseases suggest a mechanism of autoimmunity with special relevance to organ-specific diseases. This involves the local aberrant expression of HLA-DR antigens by epithelial cells and their subsequent capacity to present autoantigens occurring on their surfaces to T lymphocytes. For autoantigens which T cells recognise infrequently because of their restricted tissue location and low concentration in the circulation, T-cell tolerance is unlikely, and so induction of autoreactive T cells would occur. Because interferon is the best known inducer of DR antigen expression and viral infections may predate endocrine autoimmunity, the following sequence seems likely: local viral infection which causes interferon production, or other local environmental factors which would induce DR expression, presentation of autoantigens, and subsequent autoimmune T-cell induction. These T cells would activate effector B and T cells. Whether the initial induction of autoimmune T cells leads to autoimmune disease would depend on factors such as abnormalities of the suppressor T-cell pathway, reported to coexist with autoimmunity and necessary to induce autoimmune disease in mice. This mechanism of autoimmune disease induction explains vague associations with viral infections and long latency periods before disease becomes manifest and gives a simple explanation for the well-documented association between HLA-DR and autoimmune diseases in man.

Autoantigens↗

PubMed1991

T-lymphocyte-activating properties of epidermal antigen-presenting cells from normal and psoriatic skin: evidence that psoriatic epidermal antigen-presenting cells resemble cultured normal Langerhans cells.

Fresh and cultured human Langerhans cells display disparate functional programs, based on their capacities to activate autologous and allogeneic T cells, and with respect to their susceptibility to inhibition by transforming growth factor-beta (TGF beta). We have compared the functional properties of epidermal antigen-presenting cells (APC) procured from uninvolved and involved skin of patients with psoriasis with fresh and cultured normal epidermal cells. Freshly obtained psoriatic epidermal APC resembled cultured normal epidermal cells in their superior capacity to activate syngeneic and allogeneic T cells; fresh normal epidermal cells failed to activate syngeneic T cells, and induced only modest proliferation among allogeneic T cells. The modest T-cell--activating properties of fresh, normal epidermal cells were not suppressed by TGF beta, whereas the T-cell--activating potential of psoriatic epidermal cells, cultured normal epidermal cells, and blood APC was inhibited approximately 50% by TGF beta. Thus, fresh psoriatic epidermal APC resemble cultured normal epidermal cells functionally. Because these properties are already evident in cells obtained from uninvolved psoriatic skin, the "cultured" functional phenotype of epidermal APC in this disease may precede the appearance of active psoriatic skin lesions. Surface marker analysis of normal and psoriatic epidermal cell suspensions revealed that virtually all of the bone marrow--derived cells in normal epidermal cell suspensions were conventional (CD1+) Langerhans cells, whereas CD1+ cells comprised only a minority of bone marrow--derived (CD45+) cells in psoriatic epidermis. It is speculated that some of the CD1-, CD45+ cells in psoriatic epidermis may be Langerhans cells that have lost their "fresh" phenotype. These data indicate that an abnormality in epidermal APC function exists in psoriatic skin--even before clinical lesions develop, and we speculate that the abnormal capacity of psoriatic epidermal APC to activate syngeneic T cells may be important in the expression of keratinocyte pathology. Because psoriatic epidermal APC functions were profoundly inhibited in vitro by treatment with cyclosporin A, the effectiveness of this drug in psoriasis may be due in part to its ability to inhibit epidermal antigen-presenting cell function in vivo.

Aged↗

PubMed2005

Properties of glycolipid-enriched membrane rafts in antigen presentation.

Presentation of antigen to T cells represents one of the central events in the engagement of the immune system toward the defense of the host against pathogens. Accordingly, understanding the mechanisms by which antigen presentation occurs is critical toward our understanding the properties of host defense against foreign antigen, as well as insight into other features of the immune system, such as autoimmune disease. The entire antigen-presentation event is complex, and many features of it remain poorly understood. However, recent studies have provided evidence showing that glycolipid-enriched membrane rafts are important for efficient antigen presentation; the studies suggest that one such function of rafts is trafficking of antigen-MHC II complexes to the presentation site on the surface of the antigen-presenting cell. Here, we present a critical discussion of rafts and their proposed functions in antigen presentation. Emerging topics of rafts and antigen presentation that warrant further investigation are also highlighted.

Actins↗

PubMed2006

Differential detergent fractionation for non-electrophoretic bovine peripheral blood monocyte proteomics reveals proteins involved in professional antigen presentation.

Professional antigen presenting cells (APC), dendritic cells (DC) and their myeloid progenitors, monocytes/macrophages are critical controllers of innate and adaptive immunity. Here we show that differential detergent fractionation (DDF) analysis of bovine monocytes reveals proteins related to antigen pattern recognition, uptake and presentation to immunocompetent lymphocytes. We identify 53 bovine proteins involved in immune function of professional APC. In particular, 13 adhesion molecules, three toll-like receptors (TLR1, 6 and 8), three antigen uptake-related proteins (including mannose receptor [MR] precursor), and eight actin-like proteins involved in active endocytosis were identified. In addition, MHC class I and II-related proteins, cytokines, active substances and growth factors have been identified. We conclude that the DDF approach can provide interpretable and meaningful functional information concerning protein expression profiles associated with monocyte activation, transformation into macrophages and/or immature DC, and maturation of monocyte-derived DC in the presence of multiple bovine pathogens.

Amino Acid Sequence↗

PubMed1984

Molecular signals in antigen presentation. II. Activation of cytolytic cells in vitro after ultraviolet radiation or combined gamma and ultraviolet radiation treatment of antigen-presenting cells.

Murine low-density spleen cells have potent antigen-presenting ability in a hapten-specific cytolytic T lymphocyte (CTL) system using the hapten azobenzenearsonate (ABA). Exposure of these cells to 0.33 KJ/m2 of ultraviolet radiation (UVR) after coupling to hapten results in markedly inhibited antigen-presenting function that can be substantially corrected or bypassed by interleukin 1 (IL 1). These results have been interpreted to reflect an inhibition of Lyt-1+ T cell activation by UVR-treated APC. Treatment of these cells sequentially with 1500 rad of gamma-radiation (GR) prior to hapten coupling, followed by 0.33 KJ/m2 of UVR radiation after coupling, results in an antigen-presenting defect only minimally improved by IL 1. However, partially purified interleukin 2 (IL 2) can completely bypass or correct this defect. Thus, combined GR and UVR induces a different or more profound defect in APC function when compared to UVR alone. However, these cells do provide a signal(s) other than hapten necessary for CTL activation because ABA-coupled high density spleen cells do not activate CTL cells, even with the addition of IL 2. Fluorescence-activated cell sorter analysis demonstrates that exposure of these low density spleen cells to GR or UVR results in decreased I-A antigen expression at 24 hr than either alone. The addition of nonhapten-coupled low-density APC partially reconstitutes the ability of combined GR/UVR-treated LD-APC to present antigen, and this effect is enhanced by the administration of exogenous IL 1. This occurs despite a lack of significant accessory cell activity by the LD-APC for the ABA hapten, and indicates that combined GR/UVR-treatment of APC is not functionally equivalent to completely removing them.

Animals↗