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M Sandor

Publications and source records attributed to M Sandor.

At least 55 records · Page 3Linked to original sources
PubMed1995

Resident CD4+ alpha beta T cells of the murine female genital tract: a phenotypically distinct T cell lineage that rapidly proliferates in response to systemic T cell activation stimuli.

A population of CD4+ cells has been identified in the murine female genital tract (FGT). Phenotypic studies of FGT CD4+ cells demonstrate that they express CD3 and that the majority of these cells are alpha beta TCR+Thy-1+. Most of the Thy-1+CD4+alpha beta TCR+ cells resemble memory T cells based on their expression of CD44, L-selectin and CD45RB antigens. The vast majority of Thy-1+CD4+alpha beta TCR+ FGT cells are CD5+ and all of them are B220-. Systemic stimuli including infection with Trypanosoma brucei brucei, injection with anti-CD3 epsilon, or bacterial superantigens staphylococcal enterotoxin A or B cause a rapid accumulation of CD4+ cells in the FGT exceeding that observed for CD4+ cells in spleen and lymph nodes (LN). Expansion of the FGT CD4+ cells, which are phenotypically distinct from the splenic and LN CD4+ T cells, is due to local proliferation rather than an influx of cells from the circulation. The CD4+ population in the FGT of adult nu/nu mice is dramatically reduced, indicating its thymic dependency. In lpr/lpr mice, FGT CD4 cells do not display changes characteristic of splenic or LN CD4 cells in the same animals. These findings demonstrate that the CD4+ cells of the murine FGT are thymic dependent, but that they constitute a T cell lineage that phenotypically and, probably functionally, is distinct from other peripheral CD4+ T cell populations.

Animals↗
PubMed1994

An alternative Fc gamma-receptor ligand: potential role in T-cell development.

Fetal pre-T cells express low-affinity receptors for IgG (Fc gamma R) at a developmental stage prior to the rearrangement and expression of immunoglobulin genes. The present studies investigated the possible functional significance of Fc gamma R on fetal pre-T cells. Between 13 and 17 days of fetal development a subpopulation of T-cell receptor-, Thy-1+ thymocytes express for gamma R. The same cells contain mRNA for several forms of Fc gamma R (Fc gamma RII beta 1, beta 2, and Fc gamma RIII). Concurrently, a Pgp-1-, Thy-1-, surface-immunoglobulin- fetal thymic cell binds recombinant soluble Fc gamma R. In principle this cell can interact with the pre-T cells through this counter-receptor. To test this possibility anti-Fc gamma RII/III antibody (2.4G2) was injected into pregnant mice and then into their offspring for 6 wk postpartum. The injected antibody induced a slight increase in the proportion of CD4 or CD8 single-positive, alpha/beta T cells in the thymus. However, in fetal thymic cultures in the presence of 2.4G2 or the recombinant soluble Fc gamma R there was an accelerated differentiation of thymocytes to single-positive, CD3-bright, heat-stable antigen-dull, alpha/beta T cells. These experiments show that Fc gamma Rs are present on pre-T cells during early fetal thymic development, and that a non-IgG ligand of the Fc gamma R is expressed concurrently on Thy- fetal thymocytes. Furthermore, the presumed interaction of Fc gamma R and the alternative ligand(s) influences T-cell development. IgG binding could be an adapted function of Fc gamma Rs, and, as shown for many members of the Ig super family, these receptors may have originally served as cell-cell recognition/interaction molecules required for hematopoietic development.

Animals↗
PubMed1994

T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA.

Schistosomiasis mansoni is a disease characterized by liver and intestinal granulomas. Previous investigations in our laboratory showed that nylon wool-adherent CD4+ T lymphocytes isolated from murine hepatic schistosome granulomas express receptors for somatostatin 1-14. Moreover, somatostatin 1-14 substantially decreased IFN-gamma and IgG2a, but not IL-5 secretion by dispersed granuloma cells. This paper extends these observations by defining the somatostatin receptor (SSTR) isoform most likely expressed by granuloma inflammatory lymphocytes. Amplification of mRNA by reverse transcription PCR shows SSTR1, SSTR2, and SSTR3 mRNA in normal mouse brain and other tissues. Nevertheless, only the SSTR2 PCR product was amplified from granuloma cell RNA. The nucleotide sequence of the granuloma SSTR2 PCR product from inflammatory cells is identical to the CBA murine brain SSTR2 cDNA sequence. Granuloma-derived T cell lines, FACS-isolated granuloma CD4+ T cells, thymocytes, splenocytes, and cloned T cell lines all contain mRNA for SSTR2 by reverse transcription PCR. Moreover, both SSTR2A and the splice variant SSTR2B can be amplified from dispersed granuloma cells, granuloma T cell lines, thymocytes, and splenocytes. This is the first demonstration that inflammatory cells produce mRNA for an authentic somatostatin receptor. It is probable that the lymphocyte SSTR2 receptor mediates somatostatin-induced modulation of IFN-gamma secretion.

Animals↗
PubMed1994

Molecular evidence that granuloma T lymphocytes in murine schistosomiasis mansoni express an authentic substance P (NK-1) receptor.

Murine Schistosomiasis mansoni is a parasitic disease in which granulomas develop around the schistosome ova that lodge in the liver and intestines of the host. The granuloma eosinophils make substance P (SP), a cytokine with immunoregulatory properties. Within the granuloma SP can modulate IFN-gamma production through interaction with a substance P-like receptor. SP belongs to a family of hormones called tachykinins. Three mammalian tachykinins are SP, neurokinin A (substance K), and neurokinin B (neuromedin K). In humans and rats, there are at least three distinct tachykinin receptors designated NK-1, NK-2, and NK-3. The NK-1 receptor binds only SP with high affinity. Using reverse transcription-PCR, cDNA cloning, and sequence analysis, we showed that granulomas isolated from the liver of infected mice express an authentic SP (NK-1) receptor but have no detectable neurokinin A (NK-2) and neurokinin B (NK-3) receptor mRNA, as determined by PCR. CD4+ granuloma T lymphocytes, purified by FACS, express NK-1 receptor mRNA. Normal liver devoid of granulomas exhibited none of the three tachykinin receptor subclasses.

Amino Acid Sequence↗
PubMed1994

Expression and regulation of adhesion molecules by gamma delta T cells from lymphoid tissues and intestinal epithelium.

T cells bearing the gamma delta T cell receptor localize largely in epithelial tissues, but are also present at low frequency in organized secondary lymphoid organs. To assess the role of cell surface adhesion molecules in the traffic and tissue localization of gamma delta T cells, we compared the expression of these molecules on both alpha beta and gamma delta T cells in several lymphoid and non-lymphoid organs. In the gut epithelium, gamma delta cells express less LFA-1 (CD11a), Pgp-1 (CD44), and alpha 4 integrin than the corresponding alpha beta cells. In lymph nodes (LN) and Peyer's patches (PP), adhesion molecule expression by gamma delta cells is heterogeneous, with some of the cells having a phenotype similar to that of intraepithelial gamma delta cells and the rest expressing high levels of CD44 and L-selectin (CD62L) but lower beta 7 and alpha M290, a phenotype more like lymph node alpha beta cells. Therefore, the particular set of adhesion molecules expressed by a T cell is dependent, in part, on its anatomic location. Superimposed upon this, however, are differences in expression that are based on the type of T cell; LN and PP gamma delta T cells express less CD44 but much more beta 7, alpha M290 and ICAM-1 (CD54) than alpha beta T cells in the same organ. The differences in adhesion molecules between alpha beta and gamma delta cells are not due simply to differences in their activation status, because these molecules are regulated differently after activation through the T cell receptor (TcR)/CD3 complex. The differential expression of adhesion molecules on cells bearing a particular TcR V region suggests that distinct adhesion phenotypes may arise from prior contact with specific antigen and resultant cell activation in vivo. Lastly, the presence of high level expression of alpha 4 beta 7 and alpha M290 on L-selectinlo gamma delta cells in lymph nodes suggests that these gamma delta cells may be uniquely capable of migrating to the gut. The differences in adhesion molecule expression and regulation between gamma delta and alpha beta T cells could explain, in part, the distinct homing and tissue localization of these T cell subsets in vivo.

Animals↗
PubMed1994

Methods for studying Fc receptor expression.

In the past two decades, rapid progress has been made in the field of Fc receptors. One of the reasons for this development has been the advances and improvements in the methodologies used to detect and analyze Fc receptors. This review describes the methods used to detect the murine and human Fc receptors of the various immunoglobulin isotypes at the RNA, protein, and functional level. We have given special attention to the binding assays used to detect Fc receptors through immunoglobulins or anti-Fc receptor monoclonal antibodies as probes. The various Fc receptor types exhibit a marked heterogeneity and we present a list of reagents that can differentiate between the different Fc receptor forms. These methods can detect Fc receptors on the cell membrane, as well as the cytoplasmic and secreted forms. Recent advances in the use of PCR and RNA/DNA analyses to study Fc receptor detection, expression, and function are also reviewed. The advantages and drawbacks of the various experimental approaches are presented. In addition, an appendix provides detailed protocols for the detection of Fc receptors by confocal immunofluorescence microscopy, rosetting, cytofluorometry, immunoprecipitation, and PCR.

Animals↗
PubMed1993

Differential activation of Th1 and Th2 CD4+ cells by murine brain microvessel endothelial cells and smooth muscle/pericytes.

CD4+ Th cell infiltration into the brain and the activation by cellular elements of the central nervous system (CNS) are thought to be important steps in the initiation of CNS autoimmune diseases. T cell activation requires Ag-specific stimulation and additional costimulatory signals provided by the APC. Here we describe how murine brain microvessel endothelial (En) cells and smooth muscle/pericytes (SM/P) selectively induce the Ag-specific activation of different Th1 and Th2 CD4+ T cell clones. Th1 and Th2 cell clones were used that were specific for the same peptide Ag in the context of the same class II allotype. SM/P preferentially activated Th1 cell clones, whereas En cells activated Th2 cell clones better, as reflected by cell proliferation and production of IL-2 by SM/P-activated Th1 clones and IL-4 by Th2 clones. There was no difference in the level of expression of CD4, CD2, or LFA-1 molecules between these Th cell clones, and anti-CD4, CD2, LFA-1 or ICAM-1 mAb did not differentially affect Ag-induced proliferation among the clones. Moreover, antibody to CD28 did not influence Ag presentation by brain microvessel En or SM/P cells to Ag-specific Th1 and Th2 clones. These results suggest that: 1) different The subsets might require different signals for their activation; 2) different APC might provide different costimulatory signals for Th cell subsets; and 3) brain microvessel En and SM/P might play a differential role in induction of autoreactive T cell responses in the CNS.

Animals↗
PubMed1993

Modulation of T lymphocyte proliferation in mice infected with Schistosoma mansoni: VIP suppresses mitogen- and antigen-induced T cell proliferation possibly by inhibiting IL-2 production.

Mice infected with Schistosoma mansoni mount focal granulomatous responses around each ovum that deposits in the liver and intestinal wall. The granulomas ultimately destroy the ova while absorbing the released toxic, injurious agents. The granulomas contain T cells and other cell types, all of which are under control. For example, T lymphocyte proliferation in situ within the granulomas is probably restrained by various regulatory mechanisms. Granuloma eosinophils make VIP, and granuloma T cells have VIP receptors. Yet, the function of VIP within the granulomatous response is unknown. We studied the effect of VIP on granuloma and splenic T cell proliferation in response to Con A or soluble egg antigens (SEA). [3H]Thymidine incorporation was used to assess the rate of proliferation. VIP decreased Con A- or SEA-induced, T lymphocyte proliferation. Suppression of proliferation was most evident for T cells stimulated submaximally with mitogen or antigen. Since T lymphocyte proliferation in response to antigen or mitogen requires soluble lymphokines, we investigated the capacity of VIP to alter the expression of several lymphokines as a possible mechanism for mediating suppression of T cell proliferation. VIP decreased IL-2 production, but did not effect IL-5 or IFN-gamma release. The effect of VIP on IL-2 production was dependent on the presence of a CD4+ T lymphocyte subset. VIP could no longer modulate lymphocyte proliferation if exogenous rIL-2 was added to the cultures. The addition of neutralizing anti-IL-2 mAb, but not anti-IL-4 mAb, substantially decreased granuloma lymphocyte proliferation in response to antigen or mitogen. This suggested that granuloma T cell proliferation required endogenously produced IL-2. These findings suggest that VIP may help modulate granuloma T cell proliferation through regulation of IL-2 production.

Animals↗
PubMed1993

Lymphocyte Fc receptors: the special case of T cells.

The different cell types of the lymphoid-myeloid lineage constitutively express various Fc receptors. The exception is the T-cell lineage where most subsets express Fc receptors only during a narrow window following cellular activation. M. Sandor and R.G. Lynch summarize information which identifies a multi-level relationship between Fc receptors and clonotypic T-cell receptors and conclude that this relationship might account for the restricted expression of Fc receptors on T cells.

Animals↗
PubMed1992

In vitro and in vivo activation of murine gamma/delta T cells induces the expression of IgA, IgM, and IgG Fc receptors.

The present studies examined resting and activated murine gamma/delta T lymphocytes, in vitro and in vivo, for surface expression of FcR. Polyclonal gamma/delta TCR+ lymphocytes selectively grown from the spleen and intestine of normal mice did not express FcR when the cells were in a resting state, but when cells were activated with anti-CD3 antibody virtually all of the splenic gamma/delta lymphocytes and a large subpopulation of the intestinal gamma/delta lymphocytes expressed IgA and IgM FcR. This was confirmed by using transgenic mice. Resting gamma/delta TCR+ lymphocytes from the spleen, thymus, lymph node, and blood of gamma/delta TCR transgenic mice did not express FcR for any of the five major classes of Ig H chains. Activation of the gamma/delta TCR+ cells via the CD3/TCR complex induced high levels of IgM and IgA FcR and low levels of IgG FcR. Finally, in hepatic granulomas of schistosome-infected mice, activated gamma/delta TCR+ cells are present and express high levels of IgA and IgM FcR and low levels of IgG FcR. These investigations establish that transition of gamma/delta TCR+ lymphocytes from a resting to an activated state (triggered via the T3Ti TCR complex) is accompanied by the induction of surface membrane receptors specific for Ig H chain isotypes. The activation-linked expression of FcR on gamma/delta TCR+ lymphocytes provides potential mechanisms for coupling the functional activities of gamma/delta T lymphocytes with immune mechanisms that involve Ig molecules, such as antibody-dependent cellular cytotoxicity.

Animals↗
PubMed1992

Expression of IgA and IgM Fc receptors on murine T lymphocytes.

Fc receptors are induced on T cells following activation via the TCR. T cells that express Fc receptors transiently have the ability to use two different cognate systems: the TCR and immunoglobulins bound to the Fc receptors. The studies discussed in this article are focused on the Fc alpha and Fc mu receptors that can be induced on certain subsets of murine T lymphocytes. The article emphasizes the role of the T cell receptor for antigen in the expression of Fc alpha and Fc mu receptors on murine T cells and reviews experimental observations that suggest significant molecular heterogeneity of these Fc receptors. The finding that regulation of expression of Fc alpha receptors and Fc mu receptors on T lymphocytes is linked to cellular activation via the CD3/TCR complex implies that these Fc receptors might mediate important functions in the biology and pathology of T cells.

Animals↗
PubMed1990

IgA-induced avidity maturation of IgA Fc receptors on murine T lymphocytes.

The analysis of 30 well characterized murine T lymphocyte populations using a cytofluorometric IgA binding assay has identified many populations that are constitutive and/or inducible for IgA receptor expression, and has identified two distinct mechanisms by which IgA up-regulates the IgA-binding properties of murine T cells. Studies with lymphomas, hybridomas, Ag-specific clones and activated normal splenic T cells identified many examples of CD4 and CD8 lineage cells that constitutively expressed IgA receptors. T cell populations that constitutively expressed IgA receptors exhibited enhanced IgA binding after incubation with oligomeric IgA for 18 h. The IgA-induced up-regulation of IgA binding resulted from two distinct processes: 1) an increase in the number of surface membrane IgA binding sites and 2) an increase in the avidity of IgA binding without a change in the number of binding sites. The IgA-induced avidity increase was reflected by a 5- to 10-fold decrease in the apparent Kd. Depending on the T cell population examined the enhanced binding of IgA involved one or both of these mechanisms. T cell populations that did not constitutively express IgA receptors failed to bind IgA after prolonged incubation with oligomeric IgA suggesting that if such cells can express IgA receptors they require other signals to induce their expression. Consistent with this possibility is the finding that resting splenic T cells did not bind IgA but their activation with Con A or mAb anti-T3 resulted in high level expression of IgA receptors. These studies have identified multiple distinct mechanisms that alter the IgA-binding properties of murine T cells and are discussed in terms of their possible physiologic significance.

Animals↗
PubMed1990

CD4+ murine T cell clones that express high levels of immunoglobulin binding belong to the interleukin 4-producing T helper cell type 2 subset.

A panel of 20 murine CD4+ clones was examined for the presence of surface membrane receptors for IgA, IgM, IgD, IgE, and IgG. High level expression of multiple Fc receptors (FcRs) was found on all Th2 clones. FcR expression was low or undetected on the Th1 clones. The preferential expression of FcR on activated Th2 cells suggests potential mechanisms for immunoregulatory interactions with B cells.

Animals↗
PubMed1990

Cell surface expression of the varicella-zoster virus glycoproteins and Fc receptor.

Varicella-zoster virus (VZV) specifies the synthesis of viral glycoproteins which are important antigens for induction of the host immune response. In this report the technology of laser-activated flow cytometry has been employed to measure the membrane expression of VZV glycoproteins gpI, gpII, gpIII, and gpIV. By use of biotinylated monoclonal antibodies as probes, all four glycoproteins were demonstrated on the infected cell surface. The temporal appearance of the viral glycoproteins was defined in a time course experiment and shown to be maximal about 24 hr postinfection. The issue whether VZV induces the cell surface expression of an Fc receptor (FcR) was investigated with biotinylated nonimmune human IgG, followed by streptavidin-phycoerythrin. By this technique a 10-fold increase in fluorescence intensity was seen in the VZV-infected cells as compared to the mock-infected controls. When the experiment was repeated with purified human Fc fragment rather than whole IgG, a similar degree of binding was seen. Both the VZV glycoproteins and the VZV FcR were exquisitely sensitive to trypsin treatment (1 mg/ml); likewise, the cell surface expression of these VZV products was diminished by treatment of the infected cultures with monensin, an inhibitor of glycoprotein transport. In order to prove that VZV infection was not causing the induction of a cellular Fc gamma R, the VZV-infected and mock-infected cells were stained with monoclonal antibodies directed against each of the three human cellular IgG FcR, but no differences were observed. Therefore, the FcR activity seen in the infected culture was not due to one of the known cellular Fc gamma R.

Antigens, Viral↗