Mouse and human CD8(+) CD28(low) regulatory T lymphocytes differentiate in the thymus.

Regulatory T (Treg) lymphocytes play a central role in the control of immune responses and so maintain immune tolerance and homeostasis. In mice, expression of the CD8 co-receptor and low levels of the co-stimulatory molecule CD28 characterizes a Treg cell population that exerts potent suppressive function in vitro and efficiently controls experimental immunopathology in vivo. It has remained unclear if CD8(+) CD28(low) Treg cells develop in the thymus or represent a population of chronically activated conventional T cells differentiating into Treg cells in the periphery, as suggested by their CD28(low) phenotype.

Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility.

Regulatory T (Treg) lymphocytes play a central role in the control of autoimmune pathology. Any alteration in Treg-cell biology in mouse strains used for the study of these disorders therefore raises the question of its direct link with disease susceptibility. Paradoxically, in non-obese diabetic (NOD) mice increased numbers of Treg cells develop in the thymus.

The thymic niche does not limit development of the naturally diverse population of mouse regulatory T lymphocytes.

Thymus-derived CD4(+)Foxp3(+) regulatory T lymphocytes (Tregs) play a central role in the suppression of immune responses to self-antigens and thus avoid autoimmune disorders. It remains unclear if the specialized thymic niche controls the number of differentiating Tregs. We investigated development of murine Tregs from precursors expressing the naturally very large repertoire of TCRs.

Autoimmune regulator (AIRE)-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis.

Mutations in the gene encoding the transcription factor autoimmune regulator (AIRE) are responsible for autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome. AIRE directs expression of tissue-restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE deficiency leads to impaired deletion of autospecific T-cell precursors.

Shaping of the autoreactive regulatory T cell repertoire by thymic cortical positive selection.

The main function of regulatory T lymphocytes is to keep autoimmune responses at bay. Accordingly, it has been firmly established that the repertoire of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) is enriched in autospecific cells. Differences in thymic-positive and/or -negative selection may account for selection of the qualitatively distinct regulatory and conventional T cell (Tconv) repertoires.

Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis.

Objective: To test if interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in rheumatoid arthritis (RA).

Methods: The study included 108 patients with early RA followed up for 2 years and 128 healthy controls. From genomic DNA, 6 polymorphisms in genes for IL-1beta, IL-1Ra, IL-10, and IL-4 were typed.

Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovial membrane of multiple joints. This inflammatory microenvironment allows fibroblast-like synoviocytes (FLS) to express or enhance several adhesion or costimulatory molecules. This phenotypic shift, under proinflammatory cytokines, seems to be related to functional consequences for antigen presentation to T cells.

Residue 67 in the DRbeta1*0101 and DRbeta1*0103 chains strongly influences antigen presentation and DR-peptide molecular complex conformation.

Two closely-related molecules, DR(alpha,beta1*0101) and DR(alpha,beta1*0103), whose beta chains only differ by three amino acids at positions 67, 70, and 71, and six intermediate molecules obtained by site-directed mutagenesis were used to ascertain the respective roles of the three polymorphic residues. Substitutions at positions 70 (D-->Q), 71 (E-->R) and 67 (I or L-->F) strongly affected HA 306-318-specific T-cell recognition. The consequences of the substitution of residue 67 by a phenylalanine depended on the modified HLA-DR molecule.

Dominant clones in immortalized T-cell lines from rheumatoid arthritis synovial membranes.

Transformation of human T cells by herpesvirus saimiri allows the production of an unlimited number of T cells which express a functional T-cell receptor. In this study we transformed four T-cell lines derived from rheumatoid arthritis synovial membranes. The transformed T cells were mainly CD4+ and expressed the phenotype of activated T cells.

The human myelin oligodendrocyte glycoprotein (MOG) gene: complete nucleotide sequence and structural characterization.

Human myelin oligodendrocyte glycoprotein (MOG), a myelin component of the central nervous system, is a candidate target antigen for autoimmune-mediated demyelination. We have isolated and sequenced part of a cosmid clone that contains the entire human MOG gene. The primary nuclear transcript, extending from the putative start of transcription to the site of poly(A) addition, is 15,561 nucleotides in length.

Bone modeling in gallium nitrate-treated rats.

Gallium nitrate (GaN) reduces cancer-related hypercalcemia and inhibits bone resorption in vitro. This study investigated the effects of chronic GaN administration on bone, kidney, and parathyroid gland activity of growing rats. Experimental animals received GaN (1.

Mitochondrial calcium and bone mineralization in the rat fetus.

The initial mineralization of the tibial bone collar of 17-day-old rat fetuses has been investigated. Images obtained after glutaraldehyde-paraformaldehyde-OsO4 fixation were compared to those obtained after K-pyroantimonate (PAO) fixation. Ca, P and Sb were identified and Ca/P intensity ratios evaluated by wavelength dispersive X-ray microanalysis.

[Tubal sterility: Disturbances in haemostasis and cardiac arrest during the shirodkar manoeuvre (author's transl)].

Over a period of 10 months (august 1975 to may 1976), the authors observed 6 successive accidents during the Shirodkar manoeuvre during operations for sterility of tubal origin: 1) 4 cases involved disturbances in haemostasis only, clinical manifestations being seen in only one case. In the laboratory, these quite atypical manifestations suggested either fibrinolysis or disseminated intravascular coagulation. 2) In 2 cases there was cardiovascular collapse with cardiac arrest.

[Chronic suppuration of the breast].

We have found a series of 14 cases of chronic suppuration of the breast in 10 years in the Surgical and Gynaecological Clinic of the Salpêtrière Hospital. The symptomatology at the outset is usually innocuous, showing itself as a tumour that appears either gradually or suddenly. Diagnosis is not difficult and is usually solved by tapping the tumour.