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B Rocha

Publications and source records attributed to B Rocha.

15 recordsLinked to original sources

Selection of intraepithelial lymphocytes with CD8 alpha/alpha co-receptors by self-antigen in the murine gut.

We have studied T-cell receptor (TCR) and alpha/alpha CD8 expression in thymus-independent intraepithelial lymphocytes (TI IELs) from the gut of mice bearing transgenic (TG) TCR alpha beta specific for the male antigen, presented by H-2Db class I major histocompatibility complex (MHC) molecules. In contrast to TCR+ alpha beta cells differentiating in the thymus (from CD4+CD8+ precursors to CD4+CD8- or CD4-CD8+ progeny), TI IELs are not deleted by self-antigens, nor are they positively selected in the absence of the specific peptide. On the contrary, recognition of the antigen in the context of self-MHC is required for selection and granular differentiation of CD8+ TI IELs. Our results also show that, in contrast to the thymus, expression of the beta TG does not block expression of endogenous TCR gamma delta genes in TI IELs. The size of this gut IEL subpopulation and its difference in mechanisms of repertoire selection demonstrate the existence of a major extrathymic pathway of T-cell differentiation, the role of which remains to be elucidated.

Animals

C-fos immunoreactivity in the brain following unilateral electrical stimulation of the dorsal periaqueductal gray in freely moving rats.

C-fos immunoreactivity was used to reveal brain areas in which neurons were influenced by electrical stimulations applied to the dorsal periaqueductal gray. These stimulations were applied in freely moving rats so that the resulting behaviors could be observed. Shortly afterwards, the brains of the rats were processed for C-fos immunoreactivity. In order to determine the specificity of the brain areas thus labeled, control stimulations were applied to the ventral tegmental area of other rats. Immunoreactive cells were found surrounding the tip of the stimulation electrode within a radius of 0.5 mm. This labeled area extended further along the rostro-caudal axis than along the medio-lateral or dorso-ventral axis in the periaqueductal gray. Distally, clusters of labeled cells were found ipsilaterally in the caudal periaqueductal gray extending to the nucleus cuneiformis, and bilaterally in the locus coeruleus and supramamillary decussation. More widespread labeling was found in most hypothalamic subareas and in the lateral habenula. The labeled brain areas following ventral tegmental area stimulations were totally distinct, and comprised the medial forebrain bundle, the nucleus accumbens, the vertical limb of the diagonal band and the medial septum. The pattern of labeling produced by periaqueductal gray stimulations was therefore specific, and provided information about brain structures involved in the motivational and behavioral effects of such stimulations.

Animals

Conditioned place preference induced by Ro 16-6028, a benzodiazepine receptor partial agonist.

A place conditioning situation was used to assess the putative affective properties of benzodiazepine receptor ligands in the rat. The benzodiazepine receptor partial agonist Ro 16-6028 induced a conditioned place preference, suggesting that this compound has rewarding properties. The benzodiazepine receptor antagonist Ro 15-1788 induced neither place preference nor aversion, but prevented the place preference induced by Ro 16-6028, suggesting that the rewarding effects of Ro 16-6028 are due to its action on the benzodiazepine receptor. The benzodiazepine receptor full agonist diazepam did not induce a conditioned place preference in our hands, in contrast with previous studies. The sensitivity of place conditioning with benzodiazepine ligands to situational factors, such as the existence of a preconditioning preference, is discussed.

Animals

The extrathymic T-cell development pathway.

In normal mice, not all T-lineage cells are generated and selected in the thymus; an alternative, extrathymic, development pathway exists. Extrathymic T cells are rare in the spleen and lymph nodes, but are abundant in some tissues, such as the gut. Here, Benedita Rocha, Pierre Vassalli and Delphine Guy-Grand discuss the rules of selection of extrathymic T cells, assess the possible role of these cells in the defence of epithelial integrity and their potential role in autoimmune disease.

Animals

An unusual lineage of alpha/beta T cells that contains autoreactive cells.

In male mice that express a transgenic alpha/beta T cell receptor (TCR) specific for a male-specific peptide presented by class I Db major histocompatibility complex (MHC) molecules, we describe an unusual lineage of alpha/beta T cells that are thymus dependent but do not require selection by Db MHC molecules on thymic epithelium in the absence of the specific peptide (positive selection). These cells express the transgenic alpha/beta TCR and have the CD4-8- or CD4-8low phenotype. Cells with the latter phenotype are only detected when hemopoietic cells express both the male-specific peptide as well as Db MHC molecules. In fact, these cells are autoreactive, as they expand relatively slowly after transfer into male nude mice. Also in male but not female alpha/beta TCR transgenic mice, the CD8+ cells with the transgenic TCR bear the Pgp1 marker characteristic of mature T cells activated by antigen. CD4-8- as well as CD4-8low cells do not respond significantly when cultured with male stimulator cells but proliferate vigorously when stimulated by TCR antibodies. By this latter criterion, cells in the periphery of male alpha/beta TCR transgenic mice differ from mature male-specific T cells from female alpha/beta TCR transgenic, which become intrinsically anergic when transferred into male nude mice and cannot be stimulated significantly by TCR antibodies. Thus, intrathymic deletion does not eliminate all autoreactive T cells and it is possible that cells with an apparently "benign" autoreactivity may be involved in certain forms of autoimmunity.

Animals

Peripheral selection of the T cell repertoire.

T lymphocytes undergo selection events not only in the thymus, but also after they leave the thymus and reside in the periphery. Peripheral selection was found to be dependent on T cell receptor (TCR)-ligand interactions but to differ from thymic selection with regard to specificity and mechanism. Unlike thymic selection, peripheral selection required binding of antigen to the TCR, and it induced expansion of T cell clones. Tolerance to self antigens that are restricted to the periphery occurred through the elimination of self-reactive T cells and by the clonal anergy, which was associated with down-regulation of the alpha beta TCR and CD8.

Animals

The V beta repertoire of mouse gut homodimeric alpha CD8+ intraepithelial T cell receptor alpha/beta + lymphocytes reveals a major extrathymic pathway of T cell differentiation.

Gut intraepithelial lymphocytes (IEL) contain two independent T cell receptor alpha/beta + T cell populations, with different V beta repertoires. In DBA/2 mice (Mlsa, IE+), the CD4+ and heterodimeric alpha/beta CD8+ thymodependent T cell pool shows the same deletion of V beta 6, 8.1, and 11+ cells as found in peripheral lymphoid organs. In contrast, such deletions are not observed in the pool of IEL bearing homodimeric alpha CD8+ chains, in which these V beta families are frequently observed in high amounts. The size of this gut homodimeric alpha CD8+ IEL pool and its different V beta repertoire selection demonstrate the existence of a major extrathymic pathway of T cell differentiation with a gut-restricted localization. The large amount of the thymo-independent, homodimeric alpha CD8+ IEL found in the small bowel may contribute to a first line of defense against exogenous superantigens.

Animals

Post- thymic in vivo expansion of mature alpha beta T cells.

To discriminate whether peripheral T cell expansion is a property of pluripotent T cell precursors or of T lymphocytes precommitted to the expression of a single T cell receptor, we have evaluated the repopulation capacity of T lymphocytes expressing defined V beta gene products after transfer into syngeneic nude mice. The results showed no difference in the expansion potential of cells expressing different V beta s. The frequency of cells bearing different V beta gene products in the donor and the expanded cell populations are very similar, even when sorted populations enriched or deleted in T cells expressing a defined V beta gene product were used as a source of donor cells. These results demonstrate that peripheral T cells expressing alpha beta TCR are fully competent of extensive division in the peripheral pools.

Animals

Characterization of V beta-bearing cells in athymic (nu/nu) mice suggests an extrathymic pathway for T cell differentiation.

In the present article, the expression of the T cell receptor (TcR) beta chain and other T cell molecules was evaluated in surface immunoglobulin-negative spleen cell populations of young and old BALB/c and C57BL/6 nude mice, using a panel of monoclonal antibodies. The results obtained show that in young nude mice, most Thy-1high cells do not express other T cell markers. These mice have, however, a sizable population of Thy-1low cells with the same phenotype of alpha/beta+, CD4-CD8- thymocytes or MRL/lpr peripheral T cells, expressing predominantly genes of the V beta 8 family. The evolution of alpha/beta+ cells in aging nudes is strongly suggestive of an extrathymic pathway of differentiation of these cells since (a) the acquisition of high density TcR and CD3, as well as Thy-1 or CD4CD8 antigens at the cell surface of nude V beta+ T cells is not simultaneous; (b) alpha/beta+ cells in nude mice co-express other T cell markers at random and, even in old mice, they never completely resemble to the predominant high Thy-1+ CD3+ TcR alpha/beta+, CD4+CD8+ cells of euthymic controls; and (c) BALB/c nude T cells express V beta 11 genes, that are deleted in euthymic BALB/c mice. This latter finding may also indicate differences in the mechanisms of selection of T cells specificities in the thymus vs. the peripheral pools.

Age Factors

Characterization of rat spleen-cell populations. I. Cell interactions in the regulation of in vitro response to concanavalin A.

Spleen cells from BN rats were separated in a discontinuous density gradient. Cells from different fractions were shown to be functionally diverse, light cells enhancing DNA synthesis and cell division of the dense cell fractions, while dense cells suppressed DNA synthesis and cell division of light cells. Both these effects were also present in the absence of cell stimulation, were proportional to the number of modulating cells added to the cultures, and totally independent of the magnitude of response of controls. In Con A-stimulated cultures, mitogen dose also influenced the intensity of help and suppression. Both these effects are blocked by cell treatment with cycloheximide and can be mediated by cell supernatants. A T cell seems to be responsible for both helper and suppressor effects.

Animals