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D Guy-Grand

Publications and source records attributed to D Guy-Grand.

18 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Different expression of the recombination activity gene RAG-1 in various populations of thymocytes, peripheral T cells and gut thymus-independent intraepithelial lymphocytes suggests two pathways of T cell receptor rearrangement.

The presence of transcripts of the recombination activating gene RAG-1 was studied by in situ hybridization on selected populations of murine thymocytes, peripheral lymphocytes and gut intraepithelial lymphocytes (IEL), obtained by cell sorting. RAG-1 mRNA was found in a majority of "double-positive" (DP) thymocytes, but was absent in "single-positive" thymocytes and peripheral T lymphocytes. The only other T lineages in which about 10%-20% of the cells contained RAG-1 mRNA, and in smaller amounts, were "double-negative" (DN), T cell receptor (TcR) gamma delta- cortical thymocytes and gut CD3- IEL. These observations suggest that (a) the high expression of RAG-1 transcripts in DP thymocytes is related to the process of expansion-selection of these cells, probably accompanied by repeated TcR rearrangements, and that (b) in contrast, CD3- IEL from the gut (which are thymus independent) as well as some DN thymocytes undergo limited TcR rearrangement giving rise locally to TcR+ T cells without prior extensive process of local expansion-selection. A small percentage of peripheral B cells also contained RAG-1 mRNA, raising the possibility that this protein may also be involved in immunoglobulin class switching.

Animals↗
PubMed1992

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↗
PubMed1991

Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules.

Mouse gut intraepithelial lymphocytes (IEL), whether thymodependent (CD4+ or CD8 alpha/beta +; TCR-alpha/beta +) or thymoindependent (CD8 alpha/alpha +; TCR-alpha/beta + or -gamma/delta +), all display cytotoxic activity in a "redirected lysis assay" using anti-CD3 or anti-TCR beta or delta chains secreting hybridomas as targets; this is also observed with IEL of germ-free mice, indicating that this activity, which is absent in peripheral T lymphocytes, does not require stimulation by bacterial antigens. Perforin and granzyme transcripts are detectable in unselected gut IEL, in contrast to normal T lymphocytes of peripheral lymphoid organs. Cytological labeling (with [3H]DFP) of IEL smears reveals labeled granules (i.e., containing serine-esterases, presumably granzymes) in all subsets of gut IEL. This indicates that the gut micro-environment has an inductive role on the cytotoxic differentiation of lymphocytes of various origins when they reach the gut wall to become IEL.

Animals↗
PubMed1991

Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation.

Mouse gut intraepithelial lymphocytes (IEL) consist mainly (90%) of two populations of CD8+ T cells. One bears heterodimeric alpha/beta CD8 chains (Lyt-2+, Lyt-3+), a T cell receptor (TCR) made of alpha/beta chains, and is Thy-1+; it represents the progeny of T blasts elicited in Peyer's patches by antigenic stimulation. The other bears homodimeric alpha/alpha CD8+ chains, contains no beta chain mRNA, and is mostly Thy-1- and TCR-gamma/delta + or -alpha/beta +; it is thymo-independent and does not require antigenic stimulation, as shown by its presence: (a) in nude and scid mice; (b) in irradiated and thymectomized mice repopulated by T-depleted bone marrow cells bearing an identifiable marker; (c) in thymectomized mice treated by injections of monoclonal anti-CD8 antibody, which lead to total depletion of peripheral CD8+ T lymphocytes; and (d) in germ-free mice and in suckling mice. In young nude mice, alpha/alpha CD8 chains, CD3-TCR complexes, and TCR mRNAs (first gamma/delta) are found on IEL, while they are not detectable on or in peripheral or circulating lymphocytes or bone marrow cells. IEL, in contrast to mature T cells, contain mRNA for the RAG protein, which is required for the rearrangement of TCR and Ig genes. We propose that the gut epithelium (an endoderm derivative, as the thymic epithelium) has an inductive property, attracting progenitors of bone marrow origin, and triggering their TCR rearrangement and alpha/alpha CD8 chains expression, thus giving rise to a T cell population that appears to belong to the same lineage as gamma/delta thymocytes and to recognize an antigenic repertoire different from that of alpha/beta CD8+ IEL.

Animals↗
PubMed1991

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↗
PubMed1991

Intestinal intraepithelial lymphocytes.

Recent data on phenotype, differentiation, and functions of intestinal intraepithelial lymphocytes (IEL) in rodents and in humans are reviewed in this article. IEL form a large population of activated T cells located at the interface between the body and the septic intestinal content. Phenotypic studies indicate that IEL are mainly CD8-positive cells that contain both TCR alpha beta and TCR gamma delta cells in variable proportion depending on the species and antigenic intraluminal stimulation. Studies in experimental models suggest a dual origin, both thymus-dependent and thymus-independent of IEL, and a role of the gut epithelium in the differentiation of IEL. Functional studies allow insight on the mechanisms by which IEL can protect the intestinal epithelium or conversely, when abnormally activated, induce epithelial damage.

Animals↗
PubMed1990

Subsets of CD3+ (T cell receptor alpha/beta or gamma/delta) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood.

Intestinal intraepithelial lymphocytes (IEL) were studied, after isolation in humans, for their surface antigens with a large variety of monoclonal antibodies. They show peculiar characteristics when compared with peripheral blood lymphocytes and intestinal lamina propria lymphocytes. Although a majority of human intraepithelial lymphocytes (IEL) express an alpha/beta type of T cell receptor (TcR), 13% express a gamma/delta TcR, a percentage which was significantly higher than that found in blood and in lamina propria. In contrast to observations in mice, there was no evidence that normal human TcR gamma/delta+ intestinal IEL might use preferential variable segments of gamma genes. About 10% of human intestinal IEL expressed the alpha chain but not the beta chain of CD8, thus resembling a subset of CD8 alpha+beta- IEL, which was recently described in mice and found to be of thymoindependent origin. In addition, 10% of human IEL had a unique phenotype of immature T cells, as they bore only CD7, but no other T cell or natural killer cell markers. Finally, even the major population of IEL which expressed the usual markers of the T cell lineage (CD3, TcR alpha/beta, CD2, CD4 or CD8 alpha/beta) differed from peripheral blood T lymphocytes by their peculiar expression of surface antigens associated with activation. Indeed, 80% of IEL were CD45R0+, CD45A-, but co-expression of CD11a, CD29 and LFA-3 was inconstant. In addition, 90% of IEL expressed HML-1.

Antigens, CD↗
PubMed1990

Classification of intractable diarrhea in infancy using clinical and immunohistological criteria.

Several experimental studies have demonstrated that activated intestinal T cells can induce villous atrophy. This observation led us to examine the possible role of activated T cells in the pathogenesis of intestinal lesions in a group of 13 children with intractable diarrhea and villous atrophy of unknown origin. Immunohistochemical study showed signs of intestinal mononuclear cell activation in seven patients. These signs included a marked increase in the number of mucosal T cells, mainly TCR alpha beta+, the appearance of lamina propria interleukin-2-receptor-bearing cells, and an increased expression of HLA-DR antigens by enterocytes. No local cause of intestinal T-cell activation was found. However, four out of seven patients had extradigestive symptoms of autoimmunity, suggesting that the intestine might also be the site of an autoimmune reaction responsible for the epithelial lesions. In these patients, presence of crypt necrosis and colic extension of the lesions suggested poor prognosis. In contrast, in six other patients, no immunohistochemical evidence of mucosal T-cell activation was obtained. In the latter cases, analysis of clinical data favored the hypothesis of a primary inborn defect of enterocyte differentiation.

Atrophy↗
PubMed1990

Role of in vivo activated T cells in the mechanisms of villous atrophy in humans: study of allograft rejection.

Four children aged 6 months to 9 years received fully HLA-mismatched ABO identical small intestinal allografts. In order to monitor the rejection process and to study epithelial changes induced by intestinal T cells activated by an allogeneic reaction, iterative biopsies were performed through the ileal enterostomy and processed for histology and immunohistochemistry. Episodes of acute histological reaction were observed in all 4 patients between day 10 and 160. It was preceded by appearance of pericryptic CD3+CD4+ or CD8+ T cells of recipient origin, increasing numbers of which expressed CD25. Simultaneously, early epithelial changes were noted: increased HLA-DR expression by enterocytes and decreased mitotic rate as shown by decreased numbers of KI67+ cells in crypts. During acute histological rejection, massive infiltration of mucosa by CD25+CD3+ T-cells and activated macrophages (KIM6+CD25+), was associated with crypt necrosis and then, destruction of surface epithelium. Successful treatment of graft rejection episodes with antilymphocytic serum (2), anti-CD3 monoclonal antibody (2), anti-CD25 monoclonal antibody (1) resulted in a rapid decrease of CD3+ cells, a more progressive decrease of CD25+ and KIM6+ macrophages, reappearance of KI67+ cells in crypts followed after a variable delay by recovery of villous architecture. Chronic histological rejection was observed in 1 patient after 7 months. It was characterized by total villous atrophy, fibrosis, endarteritis, infiltration of lamina propria and epithelium by CD3+CD8+ cells, a small number of which CD25+, strong HLA-DR expression by crypt and surface epithelium, increased numbers of KI67 enterocytes. Altogether these data suggested that activated T cells can induce two types of villous atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrophy↗
PubMed1986

A monoclonal antibody specific for rat intestinal lymphocytes.

A monoclonal antibody, RGL-1, was produced by fusion of NSI myeloma cells with spleen cells of a mouse immunized with isolated rat intraepithelial lymphocytes (IEL). SDS-PAGE analysis revealed that RGL-1 precipitated two major noncovalently bound chains of about m.w. 100,000 and 125,000, and a minor component of m.w. 200,000. Examination of both tissue sections and isolated cells indicated that RGL-1 stained the majority of the lamina propria lymphocytes and IEL but only very few cells (less than 2%) in the lymphoid organs and small numbers of lymphocytes in other mucosae. In the small intestine, RGL-1 stained lymphocytes with the helper (W3/25) as well as the cytotoxic/suppressor (OX8) phenotype. The antibody reacted with 95% of the granular IEL but with less than 0.1% of the blood large granular lymphocytes. Although mature IgA plasma cells in the lamina propria were RGL-1-, some large IgA-containing cells were weakly positive. In the gut-associated lymphoid tissues (GALT), studies combining immunofluorescence and autoradiography indicated that 56 and 73% of rapidly dividing cells of mesenteric lymph nodes and of thoracic duct lymph (TDL) stained with RGL-1, respectively. In addition, 90 to 100% of the IgA-containing blasts of MLN and 75% of those of TDL were labeled by RGL-1. In contrast, rapidly dividing cells of spleen and of peripheral lymph nodes did not stain with RGL-1. Because RGL-1 can be demonstrated on both intestinal lymphocytes and their immediate precursors in the GALT, its expression may be related to the homing of lymphocytes into the gut mucosa.

Animals↗
PubMed1978

The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions.

Lymphocytes of the mouse intestinal mucosa, identified in tissue sections or purified suspensions of intraepithelial lymphocytes as T cells (gut T lymphocytes [GTL]), were studied in normal mice or in beige mice (the equivalent of the Chediak-Higashi syndrome in man, characterized by giant granules in various cell types, including mast cells). Mice were studied in normal or in germ-free conditions, or during a graft versus host (GVH) reaction resulting from the injection of parental thymocytes into lethally irradiated F1 mice, a condition leading to massive accumulation of T lymphocytes of donor origin in the host gut mucosa. In normal as well as in GVH conditions, a high percentage of the gut IE lymphocytes contain granules (up to 80% in the beige mouse). These granules have ultrastructural, hostochemical and other features resembling those of mast cell granules; in beige mice, up to 50% of them can be shown to contain histamine. Granulated T cells are also found in the lamina propria. It appears that the GTL may progressively lose their surface T antigens when the granules become more developed. Kinetics of [3H]TdR labeling of the GTL, transfer experiments with T cells of various origins, selective [3H]TdR labeling and selective irradiation of the Peyer's patches (PP), and effect of thoraic duct (TD) drainage led to the conclusion that GTL are the progeny of T cells stimulated to divide in the PP microenvironment, which endows them with a gut-homing tendency. From the PP, these cells follow a cycle, migrating to the TD and to the blood to colonize the whole intestinal mucosa, the majority of them as dividing cells undergoing a single round of traffic, with some probably able to recirculate and becoming a more long-lived variety. Antigenic stimulation within the PP is necessary for the emergence of GTL progenitors, but their gut-homing property is unrelated to the antigen as shown with fetal gut grafts, notably in GVH where grafts syngeneic to the host or donor become similarly infiltrated by GTL. On the basis of their properties and of further evidence to be reported elsewhere, it is proposed that GTL belong to a special class of T lymphocytes, related to the immune defenses of the mucosal systems in general, and capable of acting as progenitors of mucosal mast cells.

Animals↗
PubMed1978

A syndrome associating partial albinism and immunodeficiency.

Two unrelated patients with partial albinism, frequent pyogenic infections and acute episodes of fever, neutropenia and thrombocytopenia are described. Their pigmentary dilution was characterized by large clumps of pigments in the hair shafts and an accumulation of melanosomes in melanocytes. Melanocytes had few short dendritic expansions, and keratinocytes were hypopigmented. No or few Langerhans' cells were detected in skin by electron microscopy and ATP-ase reactions. This pigmentary dilution, different from all other human albinisms, resembles the unique defect of the mutant dilute (d-d) mouse. Despite the presence of an adequate number of T and B lymphocytes, the patients were hypogammaglobulinemic, deficient in antibody production and incapable of manifesting delayed skin hypersensitivity or of rejecting skin grafts. Their leukocytes did not stimulate normal lymphocytes and could not generate cytotoxic cells during mixed leukocyte reaction. T lymphocytes of one patient were unable to exert a helper effect on the maturation of B lymphocytes into immunoglobulin-containing cells following in vitro stimulation with pokeweed mitogen. This suggests that the humoral deficiency might be secondary to a defect of helper T lymphocytes. Granulocytes did not show any morphologic abnormality, and their bactericidal activity was only moderately reduced. An increased number of polymorphonuclear leukocytes with polar distribution of Concanavaline A (Con A) receptors (capping) was found in one patient and her parents. The family histories suggest that this syndrome is transmitted as an autosomal recessive character.

Albinism↗
PubMed1978

Increase in the population of duodenal immunoglobulin A plasmocytes in axenic mice associated with different living or dead bacterial strains of intestinal origin.

Various bacterial strains were tested for their ability to stimulate immunoglobulin A (IgA) plasmocytes to populate the duodenal lamina propria in axenic mice. The mice were associated with the strains for at least 4 weeks. The strains inhabiting the conventional mouse intestine and belonging to the genera Lactobacillus, Streptococcus, Eubacterium, Actinobacillus, Micrococcus, Corynebacterium, and Clostridium (including the extremely oxygen-sensitive ones) are only slightly or nonimmunogenic, whereas the strains belonging to the genera Bacteroides and Escherichia have an immunogenic effect. The same result was obtained with Bacteroides and Escherichia strains isolated from the digestive tract of other animal species. The kinetics of appearance of intestinal IgA plasmocytes are similar in axenic mice monoassociated with a stimulatory strain and in conventional mice. The association of two or more strains with axenic mice leads either to the same or a greater number of duodenal IgA plasmocytes as that obtained with the most stimulatory strain monoassociated with axenic mice. The maximum stimulation recorded in all of these trials represents about two-thirds of that observed in conventional mice and was obtained in the duodenum of gnotoxenic mice harboring four bacterial strains isolated from the conventional mouse microflora. The orally administered killed cells of two immunogenic strains, E. coli and Bacteroides sp., are as immunogenic as the living cells, provided that their concentration in the digestive tract is sufficient.

Actinobacillus↗
PubMed1975

Peyer's patches, gut IgA plasma cells and thymic function: study in nude mice bearing thymic grafts.

Nude mice have poorly developed Peyer's patches with very small or no germinal centers and little lymphoid cell proliferation, and a marked decrease in the number of gut-IgA plasma cells. Thymus grafts, which restore the T lymphocyte population of their lymphoid organs to nearly normal levels, lead to a considerable development of the Peyer's patches and of their germinal centers, assocaited with a considerable increase in gut IgA plasma cells, and in the serum IgA level. These findings are consistent with the postulated relationship between the Peyer's patches germinal center cells and the gut IgA plasma cells, and might help to explain the association of thymic defects, low serum IgA, and lack of intestinal IgA plasma cells observed in some immunodeficiency syndromes of man. Nude mice also have marked decrease in the number of lymphocytes present within the intestinal epithelium. These intraepithelial lymphocytes lymphocytes, which have been shown to be of T nature, are restored to normal numbers after thymus grafting.

Animals↗