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PubMed1998

Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.

Atherosclerosis is an inflammatory-fibrotic response to accumulation of cholesterol in the artery wall. In hypercholesterolemia, low density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima, leading to activation of endothelial cells, macrophages, and T lymphocytes. We have studied immune cell activation and the autoimmune response to oxidized LDL in atherosclerotic apo E-knockout mice. Autoantibodies to oxidized LDL exhibited subclass specificities indicative of T cell help, and the increase in antibody titers in peripheral blood was associated with increased numbers of cytokine-expressing T cells in the spleen. In addition to T cell-dependent antibodies, IgM antibodies to oxidized LDL were also increased in apo E-knockout mice. This suggests that both T cell-dependent and T cell-independent epitopes may be present on oxidized LDL. In moderate hypercholesterolemia, IgG antibodies were largely of the IgG2a isotype, suggesting that T cell help was provided by proinflammatory T helper (Th) 1 cells, which are prominent components of atherosclerotic lesions. In severe hypercholesterolemia induced by cholesterol feeding of apo E-knockout mice, a switch to Th2-dependent help was evident. It was associated with a loss of IFN-gamma-producing Th1 cells in the spleen, whereas IL-4-producing Th2 cells were more resistant to hypercholesterolemia. IFN-gamma but not IL-4 mRNA was detected in atherosclerotic lesions of moderately hypercholesterolemic apo E-knockout mice, but IL-4 mRNA appeared in the lesions when mice were made severely hypercholesterolemic by cholesterol feeding. These data show that IFN-gamma-producing Th1 cells infiltrate atherosclerotic lesions and provide T cell help for autoimmune responses to oxidized LDL in apo E-knockout mice. However, severe hypercholesterolemia is associated with a switch from Th1 to Th2, which results not only in the formation of IgG1 autoantibodies to oxidized LDL, but also in the appearance of Th2-type cytokines in the atherosclerotic lesions. Since the two subsets of T cells counteract each other, this switch may have important consequences for the inflammatory/immune process in atherosclerosis.

Animals↗

PubMed2004

Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.

Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.

Animals↗

PubMed2003

Humoral and cellular autoimmune responses in stiff person syndrome.

Stiff person syndrome (SPS) is a chronic autoimmune disease associated with humoral and cellular immune responses to glutamic acid decarboxylase (GAD) 65. Another chronic autoimmune disease, type 1 diabetes (T1D), is also associated with autoimmune responses to this antigen, but T1D patients develop SPS only extremely rarely and only a third of SPS patients develop T1D (mostly mild manifestations in adulthood). In a previous study, we described important differences between T1D and SPS in the autoimmune response to GAD 65: (1) T cells of SPS patients recognize epitopes in the middle of GAD 65 (amino residues 81-171 and 313-403), whereas patients with T1D preferentially recognize another middle (161-243) and a C-terminal region (473-555); and (2) GAD antibodies (Abs) were nearly exclusively of the Th1-associated IgG1 type in T1D, whereas SPS patients had both Th1- and Th2-associated IgG4 and IgE GAD Abs. These differences were not simply related to different HLA alleles. Fine epitope mapping revealed further distinct T cell epitopes in both diseases despite similar HLA background. Therefore, a single autoantigen can elicit different immune responses causing distinct chronic autoimmune diseases possibly related to a Th1 or Th2 bias of the disease.

Adolescent↗

PubMed1996

Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice.

BACKGROUND: Autoimmune mechanisms have been implicated in the pathogenesis of chronic ongoing myocarditis. To investigate this relation, we used an A/J mouse model inoculated with coxsackievirus B3 and determined whether myocarditis would be transferred to normal hearts that were heterotopically transplanted. METHODS AND RESULTS: Inbred 3-week-old A/J mice were inoculated intraperitoneally with coxsackievirus B3 (Nancy strain; 2 x 10(4) plaque-forming units) and housed for > 60 days. The presence of the viral genome in the myocardium was determined by the polymerase chain reaction with primers specific for the 5' end of the coxsackievirus B3 genome performed at 40, 50, or 60 days after inoculation. Normal A/J mouse hearts were transplanted into the same strain of mice without myocarditis (group A) and into mice with chronic ongoing myocarditis (group B). The hearts were evaluated histologically 2 weeks after transplantation. Conventional histological examination of infiltrated T cells and macrophages was performed, and the expression of intercellular adhesion molecule-1, major histocompatibility complex (MHC) class I antigen, and MHC class II antigen was evaluated by immunoenzymatic staining. The concentrations of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor (TNF-alpha) in the grafts were measured with an ELISA. The viral RNA genomes were not detected in the mice with chronic ongoing myocarditis, but their transplanted hearts did show myocarditis. In the hearts with induced myocarditis, infiltrated mononuclear cells consisted of CD4+ T cells, CD8+ T cells (CD4+ cell number > CD8+ cell number), and macrophages. Intercellular adhesion molecule-1, MHC class I antigen, and MHC class II antigen were expressed in the vascular endothelial cells and myocardial cells in and around the infiltrated lesions. The concentrations of IL-1 alpha and TNF-alpha in group B were significantly higher than those in group A (group A versus group B: IL-1 alpha, 125 +/- 35 versus 180 +/- 34 pg/mL; TNF-alpha, 45 +/- 15 versus 96 +/- 40 pg/mL; P < .05). CONCLUSIONS: Results suggest that an autoimmune response may play a key role in the progression of chronic ongoing myocarditis.

Animals↗

PubMed2003

Unique conformation of cancer autoantigen B23 in hepatoma: a mechanism for specificity in the autoimmune response.

The association of a specific autoantibody response with distinct disease phenotypes is observed in both autoimmune diseases and cancer. Although the underlying mechanisms remain unclear, it is likely that unique properties of disease-specific autoantigens expressed in the relevant target cells play a role. It has recently been observed that the majority of autoantigens targeted across the spectrum of systemic autoimmune diseases (but not nonautoantigens) are selectively cleaved by the cytotoxic lymphocyte granule protease granzyme B (GB), generating unique fragments not observed during other forms of cell death. Although susceptibility of a molecule to cleavage by GB strongly predicts autoantigen status, the significance of this association is unclear. We used hepatocellular carcinoma and the hepatocellular carcinoma autoantigen, nucleophosmin/B23, as a model system to define the unique features of disease-specific autoantigens in the relevant disease microenvironment. These studies revealed a striking, selective susceptibility of B23 to cleavage by GB in extracts of neoplastic liver. The increased sensitivity of tumor B23 to proteolysis by GB was accompanied by slightly increased mobility on SDS/PAGE, altered subcellular localization, enrichment of an SDS-stable oligomeric form of B23, and recognition by a conformation-specific antibody detecting a B23 epitope ending at the GB cleavage site. In vitro studies demonstrated that this unique B23 conformation and resultant increased susceptibility to cleavage by GB arise when B23 translation is initiated at methionine-7. We propose that unique features of autoantigens in the disease-relevant microenvironment may regulate susceptibility to cleavage by GB and their selection by the specific autoimmune response.

Antibodies, Neoplasm↗

PubMed1999

Cell surface expression of CD154 inhibits alloantibody responses: A mechanism for the prevention of autoimmune responses against activated T cells?

Binding of CD40 by CD154 expressed on activated T cells is a pivotal event in T cell help to B cells, macrophages, and other antigen-presenting cells. Expression of CD154 by MHC mismatched cells, in contrast to expectations, strongly suppressed alloantibody responses against the cells. This was caused by a failure of priming of antibody responses by the CD154 expressing cells. We hypothesize that this lack of response against CD154 expressing cells may represent a mechanism that has evolved to prevent autoantibody responses being generated against the CD154 antigen itself, as B cells expressing antibody reactive with CD154 would probably escape deletion on binding antigen in the bone marrow due to rescue by the simultaneous ligation of CD40.

Animals↗

PubMedDate not supplied

Characterization of a recombinant Yersinia enterocolitica lipoprotein; implications for its role in autoimmune response against thyrotropin receptor.

Autoimmune Graves' disease (GD), which is characterized by hyperthyroidism, is mediated by autoantibodies to the thyrotropin receptor (TSHR). Yersinia enterocolitica (Y.e.) has been shown to produce a lipoprotein (LP) that can cross-react with the TSHR and thus can act as a potential trigger of thyroid autoimmunity. In this study, to further characterize LP, we cloned the LP gene from Y. enterocolitica and expressed a recombinant LP. This recombinant LP was mitogenic for C3H/HeJ (LPS hyporesponsive) B cells and induced production and secretion of significant levels of IL-6 from splenocytes. A mouse antibody generated against the recombinant LP cross-reacted with TSHR as shown by western blot analysis. FACS analysis of splenocytes from mice immunized with LP revealed that LP could induce increased expression of B7.1 and B7.2. The immunomodulatory effects of LP including up-regulation of B7.1 and B7.2 coupled with its ability to induce antibodies that can cross-react with the TSHR showed several potential mechanisms by which it can cause breakdown of self-tolerance to TSHR.

Animals↗

PubMed1999

Trichloroethylene activates CD4+ T cells: potential role in an autoimmune response.

Trichloroethylene is an industrial solvent and has become a major environmental contaminant. Autoimmune-prone MRL +/+ mice were treated for up to 22 weeks with trichloroethylene in the drinking water (0, 2.5, and 5.0 mg/mL) in order to study the immunoregulatory effects of this environmental toxicant. After only 4 weeks of treatment, trichloroethylene was shown to promote the expansion of CD4+ T cells that expressed a memory/activation phenotype (i.e., CD44hi CD45RBlo) and secreted high levels of IFN-gamma, but not IL-4. In addition, trichloroethylene treatment accelerated the development of an autoimmune response in the MRL +/+ mice as evidenced by an earlier appearance of antinuclear antibodies and increased levels of total IgG2a. MRL +/+ mice treated with trichloroethylene for 22 weeks also contained antibodies specific for trichloroethylene adducts, suggesting the activation of trichloroethylene-specific T cells. The results suggest that trichloroethylene can stimulate antigen nonspecific as well as specific T cells that are capable of promoting autoimmunity in genetically predisposed individuals.

Animals↗

PubMed2003

Regulation of immune and autoimmune responses by ICOS.

Proper T cell activation and function are regulated by the innate immune system, importantly through positive and negative costimulatory molecules in the B7 superfamily. Inducible costimulator (ICOS), the receptor for B7h (also known as B7RP-1), is expressed on T cells after T cell activation. Recently, using ICOS-deficient mice, we have examined the roles of ICOS in immune responses. ICOS is required for humoral immunity. In organ-specific autoimmune responses, however, ICOS has contrast roles in different disease models. On the one hand, ICOS-/- mice exhibited extreme sensitivity to experimental autoimmune encephalomyelitis (EAE); on the other, ICOS gene deletion led to complete resistance to collagen-induced arthritis (CIA) in mice. Our work not only illustrates the complexity of immune regulation by costimulatory molecules, but also suggests novel therapeutic strategies for various autoimmune diseases.

Animals↗

PubMed1995

Relationship between an asymptomatic male genital tract exposure to Chlamydia trachomatis and an autoimmune response to spermatozoa.

The relationship between a localized genital tract humoral immune response to Chlamydia trachomatis and the presence of antisperm antibodies on the surface of motile spermatozoa in the ejaculate was examined in 227 asymptomatic male partners of infertile couples with no history of exposure to C.trachomatis. Semen and serum samples were assayed for immunoglobulin (Ig) A and IgG antibodies to C.trachomatis by enzyme-linked immunosorbent assay employing a recombinant Chlamydia-specific lipopolysaccharide fragment (Medac, Hamburg, Germany), while motile spermatozoa were tested for bound autoantibodies by immunobead binding. Semen samples from 24.7 and 10.9% of the men were positive for IgA and IgG antibodies to C.trachomatis respectively. In comparison, antichlamydial IgA was less prevalent in sera (14.5%) than in semen (P = 0.01), while antichlamydial IgG was most prevalent (21.5%) in sera (P = 0.003). In 75.0% of the men with antichlamydial IgA in their semen, this antibody was undetectable in sera obtained at the time of semen collection. Conversely, 84.0% of the men with seminal antichlamydial IgG were also IgG seropositive. Antisperm IgG and/or IgA were detected on motile spermatozoa from 16.3% of the men; their occurrence was strongly correlated with the presence of antichlamydial IgA in semen (P < 0.0001). Weaker associations between antisperm antibodies and either seminal IgG antibodies to C.trachomatis (P = 0.01) or circulating IgA and IgG antichlamydial antibodies (P = 0.03) were also observed. Men with antichlamydial IgA in their semen had a lower median sperm count (82 versus 144 x 10(6)/ml) than those men without (P = 0.003); sperm morphology and motility were comparable in both groups. These data suggest that asymptomatic male genital tract exposure to C.trachomatis is a frequent event among this population and that the presence of a humoral immune response to this organism is correlated with the development of an autoimmune response to spermatozoa.

Antibodies, Bacterial↗

PubMed2004

The effects of parasite-derived immune-suppressive factors on the cellular innate immune and autoimmune responses of Drosophila melanogaster.

Immune-suppressive factors (ISFs) introduced into larvae of Drosophila melanogaster during infection by virulent endoparasitic wasps effectively block the innate immune response mediated by blood cells (hemocytes) but have little influence on the autoimmune response made by a tumor strain in which the blood cells manifest a similar response but instead target and destroy endogenous tissues. Quantitative hemocyte analyses indicate that ISFs interfere with the immune effector responses downstream of nonself recognition, hemocyte activation and differentiation, because these responses were manifested by tumor hosts, in which the parasitoids developed. The data suggest that once activated to encapsulate aberrant tissues, the target specificity of the autoimmune-activated hemocytes, and the genetic program underlying tumor formation, cannot be blocked by parasitoid-derived ISFs, which effectively inhibit identical hemocyte-mediated responses during parasitization.

Animals↗

PubMed2006

Pathogenic consequences in semen quality of an autoimmune response against the prostate gland: from animal models to human disease.

We have recently proposed an autoimmune etiology in approximately 35% of chronic nonbacterial prostatitis patients, the most frequent form of prostatitis observed, because they exhibit IFN-gamma-secreting lymphocytes specific to prostate Ags. Interestingly, this particular group of patients, but not the rest of chronic nonbacterial prostatitis patients, also presented striking abnormalities in their semen quality. In this work, we use an experimental animal model of autoimmune prostatitis on Wistar rats developed in our laboratory to investigate when, where, and how sperm cells from autoimmune prostatitis individuals are being damaged. As in patients, a marked reduction in sperm concentration, almost null sperm motility and viability, and an increased percentage of apoptotic spermatozoa were detected in samples from animals with the disease. Prostate-specific autoantibodies as well as elevated levels of NO, TNF-alpha, and IFN-gamma were also detected in their seminal plasma. In contrast, epididymal spermatozoa remain intact, indicating that sperm damage occurs at the moment of joining of prostate secretion to sperm cells during ejaculation. These results were further supported by experiments in which mixture of normal sperm cells with autoimmune seminal plasma were performed. We hypothesize that sperm damage in experimental autoimmune prostatitis can be the consequence of an inflammatory milieu, originally produced by an autoimmune response in the prostate; a diminished prostate functionality, evidenced by reduced levels of citric acid in semen or by both mechanisms simultaneously. Once more, we suggest that autoimmunity to prostate may have consequences on fertility.

Animals↗

PubMed2004

Relationship of maternal autoimmune response to clinical manifestations in children with congenital complete heart block.

OBJECTIVE: To study the autoimmune response in mothers of children with congenital heart block (CHB) diagnosed at different ages and with different clinical manifestations. PATIENTS AND METHODS: Clinical data and sera for the determination of immunological tests were available from 104 mothers of 113 children born between 1950 and 2000 and diagnosed with CHB before the age of 16 y. Prenatal diagnosis was performed in 74 (65%) children of 65 mothers, and 39 (35%) children had postnatal diagnosis of CHB. Maternal antibodies to 52 kd and 60 kd SS-A, and to 48 kd SS-B were determined by time-resolved fluoroimmunoassay (TR-FIA) and to antinuclear antibodies (ANA) by immunoflurescense (IF). RESULTS: Out of the 65 mothers of children with in utero diagnosed CHB, 88% had antibodies to 52 kd SS-A and 83% had ANA. Antibodies to 60 kd SS-A and 48 kd SS-B were less frequently present, in 48% and in 54% of the mothers, respectively. Seven (11%) of the mothers were negative by all immunoassays. Of the 13 mothers of children with in-infancy diagnosed CHB, one mother had high-titer ANA. After 1 y of age, CHB was diagnosed in 26 children; at 1 to 6 y in 16 and after 7 y in 10 children; 1/16 and 1/10 patients had positive antibodies. In all twin pregnancies (n = 4) and in all families with recurring cases of CHB (n = 5), maternal antibodies were positive in at least one assay. The titer of 48 kd anti-SS-B antibodies was significantly higher in children with cutaneous neonatal lupus (98.1 vs 41.0; p = 0.02). All mothers whose children died before the age of 4 y (n = 8) and 85% (11/13) of mothers whose children developed cardiomyopathy had elevated antibody titers in at least one assay. However, we could not find any prognostic value of maternal antibody levels or specificities on the clinical outcome of the children with CHB. CONCLUSIONS: Although rare, late detection or postnatal progression of CHB in antibody-mediated CHB should be taken into consideration. Maternal antibody levels or specificities have prognostic effect neither on the clinical outcome of the child with CHB nor on the risk of reappearance in the same family.

Autoantibodies↗

PubMed2004

Clinical and pathophysiological significance of the autoimmune response to citrullinated proteins in rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most frequent human autoimmune disease, affecting about 1% of the adult population worldwide. A better knowledge of the autoimmune mechanisms involved is essential. We identified the epithelial targets of various autoantibodies specifically associated to RA, as variants of (pro)filaggrin. We also showed that these targets correspond to deiminated ("citrullinated") proteins, of which arginyl residues have been posttranslationally transformed into citrullyl residues by a peptidylarginine deiminase (PAD). Moreover, we and others established that citrullyl residues are indispensable elements of the epitopes recognized by these autoantibodies but only in the context of specific aminoacid sequences. We also demonstrated that these autoantibodies to citrullinated proteins (ACPA) are secreted by plasma cells of the synovial tissue and that their major targets correspond to citrullinated forms of the alpha- and beta-chains of fibrin, abundant in the tissue. These results have allowed the development of new efficient immunochemical methods for the detection of ACPA. Some of them are already commercially available. These new methods have permitted the high diagnostic value of ACPA which are present very early in the course of the disease, and also their prognostic value, to be confirmed. ACPA detection should therefore prove to be also a very valuable tool to guide the choice of therapeutic strategies, from the earliest stages of the disease. The synthesis of ACPA in the rheumatoid synovial tissue and the existence therein of a specific antigenic target constitute a strong argument for the involvement of this specific immunological conflict in the pathophysiology of RA. Indeed, it could lead to activation of effector mechanisms with pro-inflammatory effects, thus to formation in the tissue of new fibrin deposits, secondarily citrullinated. We therefore, propose a new pathophysiological model accounting for the self-maintenance and chronicity of rheumatoid inflammation. Numerous questions about the pathophysiological significance of the autoimmune response to deiminated proteins in RA remain to be answered to confirm this model.

Animals↗

PubMed1987

Effect of aging on the autoimmune response to sex accessory glands in male rats.

The effect of aging on the immune response to autoantigen of rat male accessory glands (RAG) was studied in Wistar rats. Male and female rats, 3 and 12 months old, were immunized with chemically modified RAG and heterologous antigen (human serum albumin, HSA). The study of delayed type hypersensitivity (DTH) and antibodies against RAG revealed a higher response in 12-month-old animals than in 3-month-old animals (P less than 0.005), regardless of their sexes. No differences in DTH and humoral responses to HSA were observed. Experiments on the transfer of spleen cells showed an increase in response elicited by RAG immunization in young recipients of cells from normal or immunized old syngeneic donors. On the contrary, old recipients of spleen cells from normal or immunized young donors maintained their high response the same as non-transferred old rats. Therefore, both the lymphoid cells and the environment in which the response was elicited seem to be involved in the increase of the autoimmune response.

Aging↗

PubMed2001

Control of the autoimmune response by type 2 nitric oxide synthase.

Immune defense against pathogens often requires NO, synthesized by type 2 NO synthase (NOS2). To discern whether this axis could participate in an autoimmune response, we immunized NOS2-deficient mice with the autoantigen acetylcholine receptor, inducing muscle weakness characteristic of myasthenia gravis, a T cell-dependent Ab-mediated autoimmune disease. We found that the acetylcholine receptor-immunized NOS2-deficient mice developed an exacerbated form of myasthenia gravis, and demonstrated that NOS2 expression limits autoreactive T cell determinant spreading and diversification of the autoantibody repertoire, a process driven by macrophages. Thus, NOS2/NO is important for silencing autoreactive T cells and may restrict bystander autoimmune reactions following the innate immune response.

Amino Acid Sequence↗

PubMed2007

Urinary bladder epithelium antigen induces CD8+ T cell tolerance, activation, and autoimmune response.

The effort to explore the specific autoimmune mechanisms of urinary bladder has long been hindered due to a lack of proper animal models. To better elucidate this issue, we developed a novel line of transgenic (Tg) mice, designated as URO-OVA mice, that express the model Ag OVA as a "self"-Ag on the bladder epithelium. URO-OVA mice are naturally tolerant to OVA and show no response to OVA stimulation. Adoptive transfer of naive OVA-specific T cells showed cell proliferation, activation, and infiltration but no bladder histopathology. In contrast, adoptive transfer of activated OVA-specific T cells induced OVA-mediated histological bladder inflammation. Increased mast cells and up-regulated mRNA expressions of TNF-alpha, nerve growth factor, and substance P precursor were also observed in the inflamed bladder. To further facilitate bladder autoimmunity study, we crossbred URO-OVA mice with OVA-specific CD8(+) TCR Tg mice (OT-I mice) to generate a dual Tg line URO-OVA/OT-I mice. The latter mice naturally acquire clonal deletion for autoreactive OT-I CD8(+) T cells (partial deletion in the thymus and severe deletion in the periphery). Despite this clonal deletion, URO-OVA/OT-I mice spontaneously develop autoimmune cystitis at 10 wk of age. Further studies demonstrated that the inflamed bladder contained infiltrating OT-I CD8(+) T cells that had escaped clonal deletion and gained effector functions before developing histological bladder inflammation. Taken together, we demonstrate for the first time that the bladder epithelium actively presents self-Ag to the immune system and induces CD8(+) T cell tolerance, activation, and autoimmune response.

Adenoviridae↗

PubMed1987

Adoptive transfer of suppression of the autoimmune response to rat male accessory glands: characterization of the suppressor cells.

We have examined the mechanism of suppression of autoimmunity to rat male accessory glands (RAG) by T suppressor cells. This suppression was accomplished by transfer to syngeneic rats of spleen mononuclear (SpM) cells from rats rendered unresponsive by pretreatment with low doses of a purified fraction of RAG (containing the autoantigen). The experiments demonstrated that the suppressor cells that act on the inducer phase of the suppression are cyclophosphamide (Cy) sensitive and that they can be positively selected on antigen-coated plates. On the other hand, the inducer phase T suppressor cells present on spleens coming from antigen-pretreated rats did not suppress the autoimmune response in normal recipients that had been irradiated (850 rad 137Cs) just prior to receiving the cells or injected with Cy 14 days after transfer. The results indicate that the regulation of immune response to the autoantigen of RAG is complex and that it involves the interaction of many cell types.

Animals↗