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Biomedical subjects

P Musette

Publications and source records attributed to P Musette.

32 records · Page 2Linked to original sources
PubMed1999

T-cell repertoire analysis in chronic plaque psoriasis suggests an antigen-specific immune response.

Psoriasis is a chronic inflammatory cutaneous disease of unknown etiology. Activation of T cells is thought to play a major role in the pathophysiology of psoriasis. In order to gain insight into the nature of the antigen (superantigen or nominal protein antigen) involved in psoriatic lesions, we have used a RT-PCR method to analyze the frequency of the 24 T cell receptor V beta chain (TCRBV) subfamilies and the size of the antigen-binding region (CDR3), using the immunoscope assay, in skin lesions of patients with chronic plaque-type psoriasis. Semi-quantitative analysis showed that no significant difference in V beta subfamily usage could be detected in T lymphocytes infiltrating lesional skin as compared to blood lymphocytes. Alternatively, determination of the size distribution of the CDR3 of all the V beta subfamilies revealed only in psoriatic skin a marked TCR oligoclonality defined by the presence in 3 to 5 V beta subfamilies of a single predominant CDR3 size which was associated with a unique V beta-J beta combination. Identical patterns of CDR3 length and V beta-J beta combination profiles were found in symetrical lesional sites from two psoriatic patients. This type of skewed CDR3 size profile is reminiscent of a local stimulation of T lymphocytes by nominal protein antigens. These data suggest that T lymphocytes infiltrating plaque-type psoriatic skin comprise expansions of oligoclonal T cells in response to stimulation by an antigen present in the skin.

Adult↗
PubMed1997

In vivo analysis of Fas antigen-mediated apoptosis: effects of agonistic anti-mouse Fas mAb on thymus, spleen and liver.

Fas antigen (Fas/CD95) is a cell surface receptor protein that mediates apoptosis-inducing signals. To analyze the function of Fas in vivo, we examined the effects of agonistic anti-Fas antibodies in mice. The i.p. administration of the hamster anti-mouse Fas mAb, RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given the another hamster anti-mouse Fas mAb, Jo2, rapidly died of fulminant hepatitis with hemorrhage. Histological analyses of mice given RK-8 indicated severe damage of the thymus, and moderate damage of the spleen and liver. Most of the thymocytes and some hepatocytes underwent apoptosis within 1 day of administration. Flow cytometry revealed that CD4+ T cells were more sensitive to Fas-mediated apoptosis than CD8+ T cells. At day 7 after administration, the thymus was atrophied. These in vivo effects of RK-8 were transient; the thymus was regenerated, and the liver and spleen were apparently normal 1 month after injection. The administration of RK-8 into newborn mice caused severe damage of the liver and thymus. Most of the hepatocytes died and jaundice was induced. The newborn mice died within 1 week. Most hepatocytes of newborn mice may be more sensitive to apoptosis-inducing signals through Fas than those of adult mice. These results indicated that functional Fas, which introduces the death signal in vivo, is expressed on thymocytes, CD4+ splenocytes, and some adult and most newborn mouse hepatocytes.

Animals↗
PubMed1996

Expansion of a recurrent V beta 5.3+ T-cell population in newly diagnosed and untreated HLA-DR2 multiple sclerosis patients.

We have used a PCR-based technology to study the V beta 5 and V beta 17 repertoire of T-cell populations in HLA-DR2 multiple sclerosis (MS) patients. We have found that the five MS DR2 patients studied present, at the moment of diagnosis and prior to any treatment, a marked expansion of a CD4+ T-cell population bearing V beta 5-J beta 1.4 beta chains. The sequences of the complementarity-determining region 3 of the expanded T cells are highly homologous. One shares structural features with that of the T cells infiltrating the central nervous system and of myelin basic protein-reactive T cells found in HLA-DR2 MS patients. An homologous sequence was not detectable in MS patients expressing DR alleles other than DR2. However, it is detectable but not expanded in healthy DR2 individuals. The possible mechanisms leading to its in vivo proliferation at the onset of MS are discussed.

Base Sequence↗
PubMed1996

The J beta segment of the T cell receptor contributes to the V beta-specific T cell expansion caused by staphylococcal enterotoxin B and Urtica dioica superantigens.

We have used a new polymerase chain reaction-based technique to analyze at the clonal level the CDR3 diversity and the J beta usage associated with the V beta-dependent T cell receptor (TCR) recognition of two superantigens: the staphylococcal enterotoxin B and the Urtica dioica agglutinin. Our results show that subset of J beta elements is preferentially expanded in a given V beta family, independently of the nature of the superantigen. By contrast, the CDR3 loop does not contribute significantly to the T cell expansion induced by the superantigens. We conclude that the J beta segment of the TCR beta chain, but not the CDR3 region, participates in superantigen binding, presumably by influencing the quaternary structure of the TCR beta chain.

Animals↗
PubMed1996

Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice.

The V beta 8.3-specific superantigenic lectin Urtica dioica agglutinin (UDA) was used to delete the V beta 8.3+ T cells in MRL lpr/lpr mice. In contrast to the systemic lupus erythematosus-like pathology which progresses with age in the phosphate-buffered saline-injected MRL lpr/lpr controls, UDA-treated animals did not develop overt clinical signs of lupus and nephritis. The pathogenic T cell clones thus reside within the V beta 8.3+ T cell population, which includes an expanded T cell clone described previously. Finally, UDA alters the production of autoantibodies in a sex-dependent manner.

Animals↗
PubMed1996

The pattern of production of cytokine mRNAs is markedly altered at the onset of multiple sclerosis.

Using two independent PCR-based quantification techniques, we have determined the levels of IL1 beta, IL2, IL4, IL6, IL10, IFN gamma and TNF alpha mRNA in multiple sclerosis patients at the moment of diagnosis of the disease and prior to any immunosuppressive treatment. These patients exhibit markedly reduced IL2 and IL10 mRNA expression accompanied by decreased levels of TNF alpha mRNA. Our results add to the evidence that IL10 plays a role in multiple sclerosis and suggest that decreased production of this interleukin allows the proliferation of autoreactive T cells at the onset of the disease.

Acute Disease↗
PubMed1995

T lymphocyte repertoire in Theiler's virus encephalomyelitis: the nonspecific infiltration of the central nervous system of infected SJL/J mice is associated with a selective local T cell expansion.

Theiler's virus causes, in the susceptible SJL/J mouse, a chronic demyelinating disease that resembles multiple sclerosis. Demyelination is at least in part immune mediated and coincides with the infiltration of the central nervous system by T lymphocytes. We analyzed the repertoire of the T cell receptor (TcR) beta-chain for each V beta-J beta combination, in spinal cord and spleen T cells of infected animals. All V beta families were detected in spinal cord as well as in spleen, as if the central nervous system were undiscriminantly invaded by T cells in the infected animals. Some T cells, defined by specific V beta-J beta combinations, were expanded in the spinal cord but not in the spleen, most probably because of an antigen-driven response. The TcR beta-chain repertoire of infiltrating T cells was the same at the onset of demyelination as when the disease was full-blown. These results provide the first description of the repertoire of the T cells which infiltrate the central nervous system during the course of this disease.

Animals↗
PubMed1994

The expansion of a CD4+ T cell population bearing a distinctive beta chain in MRL lpr/lpr mice suggests a role for the fas protein in peripheral T cell selection.

MRL lpr/lpr mice suffer from a systemic lupus erythematosus-like autoimmune disease. The lpr mutation impairs the normal transcription of the fas message, the product of which mediates apoptosis and presumably the proper selection of T cells. We have found an early expansion of CD4+ T cells bearing a distinctive V beta 8.3-D beta 1.1-J beta 1.1 T cell receptor beta chain in the periphery of MRL lpr/lpr mice, which was not detected in MRL +/+ mice nor in the thymus of MRL lpr/lpr mice. Thus, since thymic selection is normal in MRL lpr/lpr mice, we propose that the lpr mutation results in defective negative selection at the periphery.

Animals↗
PubMed1991

Wegener autoantigen and myeloblastin are encoded by a single mRNA.

Myeloblastin is a serine protease that has been identified in the human leukemia cell line HL-60. Down-regulation of this protease can inhibit proliferation and induce differentiation of promyelocyte-like human leukemic cells. Proteinase 3, a serine protease of human neutrophils, has been identified as the Wegener autoantigen. A high level of homology between myeloblastin and proteinase 3 has suggested that they may be a single serine protease. We have recently completed the 5'-terminal nucleotide sequence of proteinase 3 and shown that its mRNA was also expressed in HL-60 cells and in cells from patients with acute myeloid leukemia. Here we demonstrate that myeloblastin and proteinase 3 are encoded by a single mRNA.

Autoantigens↗