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Biomedical subjects

J Rossert

Publications and source records attributed to J Rossert.

At least 55 records · Page 3Linked to original sources
PubMed1993

Cellular immunity in interstitial nephropathy.

Inflammatory tubulointerstitial nephritis (TIN), either as a primary or as a secondary event, plays an essential role in the development of all forms of chronic renal failure. Experimental models of TIN should help in understanding TIN in humans. As in experimental glomerulopathies, the target antigen can be a kidney structural antigen, from the tubular basement membrane (TBM) or not, or a foreign antigen. While some models are due to deposits of free antibodies or circulating immune complexes, many others involve cell-mediated immunity. This last aspect explains the importance and the originality of experimental TIN.

Animals↗
PubMed1991

HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. I. In vitro characterization of T cells involved.

Mercuric chloride (HgCl2) induces in Lewis (LEW) rats a non-antigen-specific immunosuppression and is able to down-modulate experimental allergic encephalomyelitis in about 70% of the rats. The aim of the present study was to determine the frequencies of lymph node cells involved in the proliferative response to myelin basic protein in rats injected with HgCl2 and immunized with myelin by using limiting dilution analysis (LDA). Highly frequent CD8+ T suppressor cells and at least 10-fold less frequent protein basic-specific T helper cells were detected in these rats. A third cell type allowing the proliferative response of Th cells in spite of Ts cells was also demonstrated. These cells, which could act as contrasuppressor cells, were CD4+ and adhered to Vicia villosa lectin; their frequency was in the same range as that of T helper cells. These data illustrate the potential role of different levels of T cell immunoregulatory activity in autoimmunity and the major interest of LDA in their analysis.

Animals↗
PubMed1991

HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. II. In vivo demonstration of the role of T suppressor and contrasuppressor cells.

In the companion paper (J. Rossert et al., Cell. Immunol. 137, 1991), we showed by using limiting dilution analysis that Lewis (LEW) rats injected with HgCl2 and immunized with myelin (LEWHg/MYE) exhibit anti-basic protein CD4+ T helper cells (Th), at least 10-fold more frequent CD8+ T suppressor cells (Ts), and T contrasuppressor cells (Tcs). These Tcs cells were shown to be CD4+ T cells adhering to Vicia villosa (VV) lectin and allowed Th cells to proliferate despite the presence of Ts cells. The CD8+ Ts cells might be responsible for the protection from experimental allergic encephalomyelitis (EAE) observed in about 70% of LEW rats injected with HgCl2. The concomitant presence of CD4+ Tcs cells might explain that 30% of the rats escaped this protection. The aim of this work is to demonstrate in vivo the roles of CD8+ Ts cells and Tcs cells in mercury-induced protection from EAE. It will be shown that LEWHg/MYE rats depleted of CD8+ cells as well as LEWHg/MYE rats transferred with VV lectin-adherent Tcs cells develop EAE. These data demonstrate that CD8+ Ts cells are responsible for HgCl2-induced protection and that Tcs cells are involved in the control of Ts cells in vivo.

Animals↗
PubMed1991

[Immunosuppressive drugs and autoimmune diseases].

Only a few immunosuppressive drugs can be used today. These are: corticosteroids, azathioprine, cyclophosphamide, ciclosporine A, accessorily chlorambucil and methotrexate. They all have different actions on immune responses. The use of these drugs has completely changed the prognosis of autoimmune diseases such as systematic lupus erythematous, polyartheritis nodosa, Wegener's granulomatosis. Nevertheless treatment of other autoimmune diseases, such as type I insulin-dependent diabetes mellitus or multiple sclerosis, has been inconclusive.

Autoimmune Diseases↗
PubMed1990

Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat.

In Brown-Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti-glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B-cell polyclonal activation probably due to frequent anti-class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti-class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgCl2 provokes the appearance of non-antigen-specific CD8+ T cells responsible for a depression of T-cell functions. The aim of this work was to test the effect of treatment with an anti-CD8 monoclonal antibody (MoAb) in both BN and LEW rats. Anti-CD8 MoAb-treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury-induced autoimmunity were modified in BN rats. Mercury-induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats the appearance of rare anti-class II T cells showing that these cells are normally present in that strain but negatively controlled by suppressor T cells.

Animals↗
PubMed1989

[Is necrotizing vasculitis a disease caused by deposits of circulating immune complexes?].

From findings in serum sickness, it has often been considered that circulating immune complexes play a crucial role in the pathogenesis of experimental necrotizing vasculitis and glomerulonephritis. In reality, most cases of experimental vasculitis might well be due to the formation of immune complexes in situ. Moreover, the role of cell-mediated immunity, still poorly studied, might be important. In humans, the respective roles of circulating immune complexes, immune complexes formed in situ and cell-mediated immunity remain imperfectly known.

Animals↗
PubMed1989

Tamm-Horsfall protein accumulation in glomeruli during acetazolamide-induced acute renal failure.

A patient with ocular hypertension was treated with acetazolamide. Acute renal failure developed rapidly and renal biopsy showed mild tubular lesions and crystal formation in a tubular lumen. By immunofluorescence studies with a monoclonal antibody, Tamm-Horsfall protein, normally absent from the proximal segments of the nephron, was detected in most glomeruli. This strongly suggests that tubular obstruction plays a major part in some cases of acetazolamide-induced acute renal failure.

Acetazolamide↗
PubMed1989

[Immune glomerulopathies of toxic origin. Possible mechanisms of induction].

Mechanisms of toxic-induced autoimmunity including drug-induced autoimmune glomerulonephritis are unknown. In the mercury-induced autoimmune disease in Brown-Norway (BN) rats it has been shown that B cells are polyclonally activated provided that T cells are present. Autoreactive T cells that recognized self-Ia on normal B cells have been found to be highly frequent in HgCl2-injected BN rats. It has been possible to transfer all the autoimmune abnormalities by injecting T cells from HgCl2-exposed BN rats into normal syngeneic animals. However the recipient had to be depleted in suppressor/cytotoxic T cells by treatment with an anti-CD8 antibody for a full-blown disease to appear. These experiments show that a toxic agent may induce an autoimmune glomerulonephritis in the context of an autoimmune disease by generating or expanding anti-self Ia autoreactive T cells provided that suppressor/cytotoxic T cells have been inhibited. Autoreactive T cells are probably responsible for the polyclonal activation of B cells in this model. This mechanism does not rule out that other mechanisms could play a role.

Animals↗
PubMed1988

Autoreactive T cells in mercury-induced autoimmunity. Ability to induce the autoimmune disease.

It has been previously shown that autoreactive T cells appear during mercury-induced autoimmunity in Brown-Norway (BN) rats. In the present work, it is shown that: 1) T cells and T helper cells from HgCl2-injected BN rats are able to actively transfer autoimmunity in normal BN rats; the disease transferred is exacerbated when recipients are treated with the antisuppressor/cytotoxic T cell monoclonal antibody (OX8); 2) normal T cells preincubated with HgCl2 are also able to transfer the disease in OX8-treated but not in T cell-depleted rats; and 3) T cells from HgCl2-injected BN rats also transferred the disease in both normal and T cell depleted rats. It is concluded that: 1) autoreactive T cells, and presumably anti-Ia T cells are involved in the pathogenesis of mercury-induced autoimmunity; 2) these autoreactive T cells induce suppressor/cytotoxic T cells to proliferate in normal syngeneic recipients; the fact that this T cell subset did not proliferate in HgCl2-injected BN rats suggests that HgCl2 also affects T suppressor cells; and 3) mercury-induced autoimmunity could result from the additive effect of the emergence of autoreactive T cells and of a defect at the T suppressor level.

Animals↗
PubMed1988

Effect of HgCl2 on experimental allergic encephalomyelitis in Lewis rats. HgCl2-induced down-modulation of the disease.

HgCl2 induces autoimmunity in Brown-Norway rats and immunosuppression in Lewis rats. In the latter rats, HgCl2 triggers the proliferation of T suppressor/cytotoxic (OX8+) cells which actively suppress T cell functions. This led us to study the effect of HgCl2 on experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease obtained following immunization with basic protein (BP). It will be shown that HgCl2 attenuates or even prevents clinical manifestations of EAE and inhibits both the proliferative response of T cells to BP and the anti-BP antibody response. This immunosuppression was not due to a defect at the T helper cell or antigen-processing cell level but to the emergence of T suppressor cells.

Animals↗
PubMed1988

Autoreactive T cells in mercury-induced autoimmunity. Demonstration by limiting dilution analysis.

Mercuric chloride is responsible in Brown-Norway rats for an autoimmune disease that is autoregulated. Previous studies have shown that this agent induces T cell-dependent polyclonal B cell activation in these rats. Evidence has also been obtained for the existence of autoreactive T cells which play a role in the evolution of this process. In the present study, limiting dilution analysis was used to demonstrate that (a) frequent autoreactive T helper cells which proliferate in the presence of T cells from HgCl2-injected rats are present from day 4; (b) frequent auto-anti-Ia T helper cells which recognize normal B cells as well as B cells from HgCl2-injected rats appear from day 6; and (c) less frequent T suppressor cells which could play a role in autoregulation emerge from day 14.

Animals↗
PubMed1988

Efficacy of intravenous spiramycin in the treatment of severe Legionnaires' disease.

Spiramycin is a 16-membered macrolide that has been shown in cell and animal models to be active against Legionella spp. The activity of the injectable form of spiramycin was evaluated in the treatment of severe Legionnaires' disease in seven immunocompromised and three previously healthy patients. Seven of the ten patients were cured. Three patients died primarily from the underlying disease or from intercurrent complications. This result and the better tolerance of spiramycin compared with 14-membered macrolides suggest that spiramycin may be a suitable alternative to erythromycin for the treatment of Legionnaires' disease.

Adult↗
PubMed1987

HgCl2 induces nonspecific immunosuppression in Lewis rats.

Brown-Norway (BN) rats injected with HgCl2 have been previously shown to develop a variety of autoimmune abnormalities. The susceptibility of BN rats is genetically controlled, and Lewis rats bearing a different RT1 haplotype are resistant. It will be shown in the present study that the number of MRC OX-8+ (suppressor/cytotoxic) cells increases in the spleen and lymph nodes of Lewis rats injected with HgCl2. The responsiveness to T cell mitogens and to alloantigens is concomitantly inhibited. Spleen cells from Lewis rats injected with HgCl2 fail to induce a local graft-vs.-host reaction. Data presented show that MRC OX-8+ cells are involved in the immunosuppression in Lewis rats treated with HgCl2. Furthermore, lymph node cells and MRC OX-8+ cells from these rats are able to inhibit the normal mixed lymphocyte reaction indicating that suppression is active. Thus, HgCl2 is able to trigger immune dysregulation leading either to autoimmunity or to immunosuppression depending upon the genetic background of the rat strain tested.

Animals↗