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Biomedical subjects

J L Andreu

Publications and source records attributed to J L Andreu.

30 records · Page 2Linked to original sources
PubMed1991

Selective expansion of T cells bearing the gamma/delta receptor and expressing an unusual repertoire in the synovial membrane of patients with rheumatoid arthritis.

In a study of 7 patients with rheumatoid arthritis (RA), we characterized the T cell population present in the synovial membrane, thought to be the location where T cells trigger the disease. Synovial membrane lymphocytes from the RA patients were found to have a selective expansion of gamma/delta T cells (8.8% in synovial membrane versus 4% in peripheral blood). Expansion of the gamma/delta T cell subset was not found in the synovial membrane of patients with osteoarthritis. We characterized the gamma/delta T cell repertoire using monoclonal antibodies Ti gamma A, BB3, and delta TCS1, which recognize the gene products encoded by V gamma 9, V delta 2, and V delta 1-J delta 1, respectively. The majority of the synovial gamma/delta T cells did not express the repertoire encoded by these genes, which is found in nearly 100% of the peripheral blood gamma/delta T cells of healthy volunteer donors and in the thymus at early stages of development. We conclude that the synovial membrane of patients with RA displays a selective expansion of a specific population of gamma/delta T cells expressing a clonotypic receptor not yet serologically defined, which might be implicated in the development of the disease.

Adult↗
PubMed1991

Treatment with IL2/vaccinia recombinant virus leads to serologic, histologic and phenotypic normalization of autoimmune MRL/lpr-lpr mice.

We have analyzed the effect of IL2 administered in vivo on both the lymphoproliferation and autoimmune disease progression of MRL/lpr mice. Human IL2 was delivered by infecting MRL/lpr mice with vaccinia virus recombinants at different stages of lpr disease. The results reported here showed that treatment of lpr mice with IL2 mediated: (1) restored normal thymic differentiation illustrated by an expansion of the double positive population accompanied by increased numbers of mature thymocytes; (2) depletion of the peripheral CD3+ CD4- CD8- (DN) T-cell population; (3) normalization in the pattern of TcRV beta gene expression displayed by mature T cells; (4) decreased urine-protein levels and immune complex deposition in the kidney, with a resultant absence of glomerulonephritis; and (5) an increased longevity (from 195 to more than 400 days). We speculate that the dramatic reduction in the abnormally expanded CD3+ DN T-cell population following IL2 therapy might be directly related to the amelioration and/or prevention of autoimmune disease in these mice. Collectively, these results suggest that diseases showing a selective expansion of DN cells should be envisaged as possible targets for the treatment described here.

Animals↗
PubMed1990

Recovery from autoimmunity of MRL/lpr mice after infection with an interleukin-2/vaccinia recombinant virus.

Interleukin-2 (IL-2) is a T-cell derived molecule implicated in the clonal expansion of antigen-activated T cells and in T-cell development. IL-2 is also implicated in autoimmune disease, although its role is still controversial. Murine systemic lupus erythematosus (SLE) is a good model for human SLE as most of the immunological abnormalities in the human disease also seem to be operative in the mouse. Among SLE mice, the MRL/lpr strain develops early in life autoimmune diseases such as immune complex-mediated glomerulonephritis, arthritis and arteritis. Lymphoid abnormalities associated with those diseases in this strain are thymic atrophy and abnormal proliferation of CD3+ CD4- CD8- 'double-negative' T cells, resulting in massive generalized lymph node enlargement. We have therefore now examined the effects of IL-2 on the disease progression in MRL/lpr mice using live vaccinia recombinant viruses expressing the human IL-2 gene. Vaccinated mice showed prolonged survival, decreased autoantibody and rheumatoid factor titres, marked attenuation of kidney interstitial infiltration and intraglomerular proliferation, as well as clearance of synovial mononuclear infiltrates. Inoculation with the IL-2/vaccinia recombinant virus led, in addition, to drastic reduction of the double-negative T-cell population, improved thymic differentiation and restoration of normal values of mature cells in peripheral lymphoid organs.

Animals↗
PubMed1990

Inside the thymus, Mls antigen is exclusively presented by B lymphocytes.

The ability to stimulate an Mls-1 mixed lymphocyte reaction (MLR) is predominantly expressed by low density B lymphocytes in the spleen and peritoneal cavity of normal adult mice, and is absent in splenic B cells 1 month after lethal irradiation and reconstitution from autologous bone marrow. Coreconstitution of these mice with normal syngeneic peritoneal cells restores the stimulatory potential of splenic B cells, but sorted CD5+ or CD5- IgM+ lymphocytes from peritoneum are equally good stimulators, suggesting that functional Mls-1 expression may require long life spans and selection. Bone-marrow-reconstituted DBA/2 mice that fail to express Mls-1 antigens in the periphery nevertheless maintain T-cell receptor V beta 6 and 8.1 deletions among the newly formed T cells. These findings led us to directly investigate the Mls stimulatory ability of purified antigen-presenting cell populations inside the thymus. We report here that thymic B lymphocytes seem to represent the only intrathymic cell population able to stimulate Mls-1 MLR.

Animals↗
PubMed1989

Further evidence for coelomic-associated B lymphocytes.

Previous observations indicate that "CD5 B lymphocytes" are preferentially clustered in gut-related mesenchymal areas, such as peritoneum, thymus and tonsils. We have now found that pleuropericardial spaces contain an homogeneous population of large-sized, noncycling, nonsecretory B cells, expressing very high levels of surface IgM, little or no IgD, Mac-1 and low levels of B220. This phenotype and the over-representation of some antibody clonotypes suggest that the pleuropericardial cavity contains a pure "CD5 B cell" population. In all mouse strains analyzed, however, many of these cells are CD5-. These findings, together with the common origin of peritoneum and pleural layers in the primitive coelomic cavity, suggest that such B cells differentiate locally from intraembryonic precursors; we propose to designate them as "coelomic", to distinguish them from "stromal", bone marrow-derived B cells.

Animals↗
PubMed1989

Felty's syndrome: response to low dose oral methotrexate.

We describe a case of Felty's syndrome with persistent severe neutropenia below 200 granulocytes/mm3, splenomegaly and repeated infections. The patient did not respond to treatment with intramuscular gold salts and lithium carbonate. After 2 months of oral methotrexate administration, 7.5 mg weekly, clinical improvement was notable: she remained afebrile, neutropenia disappeared and splenomegaly regressed. This clinical and laboratory improvement persisted 5 months later. Moreover, accidental discontinuance of the drug and later readministration supported the evidence that the improvement was due to methotrexate.

Administration, Oral↗