PubMed Health⌕ Search

Biomedical subjects

E Reinherz

Publications and source records attributed to E Reinherz.

16 recordsLinked to original sources
PubMed2001

T cell responses modulated through interaction between CD8alphaalpha and the nonclassical MHC class I molecule, TL.

The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind CD8alphabeta, TL preferentially binds the homotypic form of CD8alpha (CD8alphaalpha). Thus, TL tetramers react specifically to CD8alphaalpha-expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8alphabeta, which recognizes the same MHC as the T cell receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8alphaalpha to TL modifies responses mediated by TCR recognition of antigen presented by distinct MHC molecules. These findings define a novel mechanism of lymphocyte regulation through CD8alphaalpha and MHC class I.

Amino Acid Motifs↗
PubMed2001

Expression of endothelial nitric oxide synthase in the ischemic penumbra: relationship to expression of neuronal nitric oxide synthase and vascular endothelial growth factor.

Expressional patterns of the endothelial and neuronal forms of nitric oxide synthase (NOS) in cerebral ischemia were studied utilizing a permanent middle cerebral artery occlusion (PMCAO) model. Motor performance and infarct volumes were determined in the rats. Immunohistochemical staining for eNOS, nNOS and neurofilament were performed at 1, 2, 3, 5, 7 and 14 days after PMCAO. Vascular endothelial growth factor (VEGF) expression was determined by in-situ hybridization. PMCAO caused a reproducible cortical infarct with motor deficits in the rats. Double immunohistochemical stainings indicated that eNOS and nNOS were induced in ischemic neurons. Most stained neurons were positive for both NOS forms but some reacted with only one NOS antibody. nNOS expression peaked at 24-48 h after PMCAO, stained mainly the cytoplasm of core neurons, and disappeared after the 3rd day. eNOS expression increased until the 7th day, stained mainly the cytoplasm and membrane of penumbral cells and disappeared by the 14th day after PMCAO. VEGF expression was significantly induced in the penumbral zone in a similar distribution to eNOS. The anatomical and temporal pattern of VEGF and eNOS induction in the brain after permanent ischemia suggest that these mediators may play a role in protecting penumbral tissue from additional ischemic damage.

Animals↗
PubMed2000

T Cell Receptor Binding to a pMHCII Ligand Is Kinetically Distinct from and Independent of CD4.

Immune recognition of pMHCII ligands by a helper T lymphocyte involves its antigen-specific T cell receptor (TCR) and CD4 coreceptor. We have characterized the binding of both molecules to the same pMHCII. The D10 alphabeta TCR heterodimer binds to conalbumin/I-A(k) with virtually identical kinetics and affinity as the single chain ValphaVbeta domain module (scD10) (Kd = 6-8 microm). The CD4 ectodomain does not alter either interaction. Moreover, CD4 alone demonstrates weak pMHCII binding (Kd = 200 microm), with no discernable affinity for the alphabeta TCR heterodimer. Hence, rather than providing a major contribution to binding energy, the critical role for the coreceptor in antigen-specific activation likely results from transient inducible recruitment of the CD4 cytoplasmic tail-associated lck tyrosine kinase to the pMHCII-ligated TCR complex.

Antigen Presentation↗
PubMed1999

Circulating CD2+ monocytes are dendritic cells.

Low levels of CD2 have been described on subsets of monocytes, macrophages, and dendritic cells. CD2 is expressed on about one-third of circulating monocytes, at levels one-half log lower than on T or NK cells, representing 2-4% of PBMC. FACS analysis of CD2+ and CD2- monocytes revealed no significant difference in the expression of adhesion molecules (CD11a/b/c), class II Ags (HLA-DR, -DQ, -DP), myeloid Ags (CD13, CD14, CD33), or costimulatory molecules (CD80, CD86). Freshly isolated CD2+ and CD2- monocytes were morphologically indistinguishable by phase contrast microscopy. However, scanning electron microscopy revealed large prominent ruffles on CD2+ monocytes in contrast to small knob-like projections on CD2- monocytes. After 2 days of culture, the CD2+ monocytes largely lost CD14 expression and developed distinct dendrites, whereas the CD2- monocytes retained surface CD14 and remained round or oval. Freshly isolated CD2+ monocytes were more potent inducers of the allogeneic MLR and more efficiently induced proliferation of naive T cells in the presence of HIV-1 gp120 than did CD2- monocytes. After culture in the presence of GM/CSF and IL-4, CD2+ monocytes were up to 40-fold more potent than monocyte-derived dendritic cells or CD2- monocytes at inducing allogeneic T cell proliferation. These findings suggest that circulating CD2+ and CD2- monocytes are dendritic cells and the precursors of macrophages, respectively. Thus, dendritic cells are far more abundant in the blood than previously thought, and they and precursors of macrophages exist in the circulation as phenotypically, morphologically, and functionally distinct monocyte populations.

Antigen Presentation↗
PubMed1985

Proliferative responses of circulating human NK cells: delineation of a unique pathway involving both direct and helper signals.

The present studies were performed to investigate mechanisms of human natural killer (NK) cell activation. NK-active cells were purified out of heterogeneous large granular lymphocytes (LGL)-enriched suspensions using a "pan NK"-specific monoclonal antibody termed anti-NKH1A. It was found that treatment of NKH1A+-sorted cells by T lymphocyte mitogens such as phytohemagglutinin (PHA) or anti-T11(2) plus anti-T11(3) did not induce proliferative responses. In fact, there was no measurable interleukin 2 (IL2) secretion and no significant increase in IL2 susceptibility following incubation with either PHA or anti-T11(2) plus anti-T11(3). However, as opposed to small resting T lymphocytes, NKH1A+ cells moderately proliferated in the presence of IL2. This IL2-dependent proliferation was dramatically increased after interaction between NK-active lymphocytes and certain hematopoietic cell lines such as K562 or EBV-transformed lymphoblastoid cell lines. These studies indicate that unique activation mechanisms can be identified when NK lymphocytes are purified out of LGL-enriched fractions. The NK activation pathway delineated here appears essentially distinct from those described for T lymphocytes. Indeed the nature of the NK cell/inducing cell interaction is unknown and triggering cannot be related, for example, to a conventional allogeneic effect mediated through membrane exposure of class I or class II major histocompatibility complex gene products. Moreover, these interactions do not lead to the development of autocrine responses. Together the present results support the view that direct signals can preactivate NK cells but are not sufficient to trigger proliferation which must therefore be regulated by helper populations.

Antibodies, Monoclonal↗
PubMed1985

Systemic lupus erythematosus: delineation of subpopulations by clinical, serologic, and T cell subset analysis.

Patients with systemic lupus erythematosus (SLE) (n = 194) were analyzed for correlation of clinical features. In addition, the proportions of the two major T cell subsets were determined in 87 subjects. Two patient subgroups were discerned: one in which severe renal disease, leukopenia, and thrombocytopenia predominated, and a second in which sicca syndrome and involvement of the central nervous system, lungs and muscle occurred. The ratio of T helper/inducer to T suppressor/cytotoxic cells was reduced in the first group and increased in the second. We conclude that SLE does not comprise a single disease entity, but rather represents a number of syndromes with overlapping clinical features. The correlation of clinical symptoms with the proportions of circulating T cell subsets suggests that several immunologic mechanisms may underlie the various types of SLE.

Adult↗
PubMed1983

Circulating lymphocyte populations in Hodgkin's disease after mantle and paraaortic irradiation.

The effect of mantle and paraaortic radiation on peripheral blood lymphocytes was studied in 11 previously untreated patients with early stage Hodgkin's disease using a series of monoclonal antibodies defining immunoregulatory lymphoid cells. Immediately following the completion of radiotherapy, there was a significant reduction in the number of lymphocytes and the percent of circulating T cells. This acute decrease in T cells was due to a marked diminution in the number of inducer T cells, while the fraction of suppressor T cells remained constant. These changes persisted for up to 12 mo and were accompanied by a later increase in the fraction of circulating B lymphocytes and cells bearing surface Ia. It thus appears that mantle and paraaortic radiotherapy causes a relatively selective reduction in the inducer T-cell population. The implications of a change in the ratio of inducer to suppressor T cells is discussed.

Antibodies, Monoclonal↗
PubMed1983

Identification of circulating maternal T and B lymphocytes in uncomplicated severe combined immunodeficiency by HLA typing of subpopulations of T cells separated by the fluorescence-activated cell sorter and of Epstein Barr virus-derived B cell lines.

Circulating maternal T cells were sought in a child with severe combined immunodeficiency (SCID) and no evidence of acute graft-vs-host disease, but who had small numbers (9 to 11%) of circulating T3-positive cells. HLA typing of unfractionated peripheral blood lymphocytes (PBL) and of isolated E rosette-forming cells (37 to 44% of PBL) failed to reveal the presence of maternal lymphocytes. T3-positive cells isolated by the fluorescence-activated cell sorter, however, expressed exclusively maternal HLA antigens. A lymphoblastoid B cell line established by infecting the patient's PBL with Epstein Barr virus then expressed exclusively maternal HLA antigens. The presence of maternal T and B cells in uncomplicated SCID may be more common than thought previously and calls for a careful assessment of the origin of any mature T cells that are present in affected infants. In addition, the presence of maternal cells in SCID may complicate the infant's therapy.

B-Lymphocytes↗
PubMed1981

Characterization of T cell surface glycoproteins T 1 and T 3 present on all human peripheral T lymphocytes and functionally mature thymocytes.

The monoclonal antibodies, anti-T1 and anti-T3, both react with all human peripheral thymus-derived lymphocytes and with 10% of thymocytes; each, however, recognizes different cell surface structures. It was determined that the target antigen of anti-T is a 69 000 molecular weight cell surface glycoprotein and that the T3 antigen is a 19 000 mol. wt. glycoprotein.

Borohydrides↗
PubMed1981

Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10.

Three human thymic cell-surface antigens T6, T9 and T10, previously defined by monoclonal antibodies, were analyzed using immunoprecipitation techniques. The antigen T6 was found to be a 49,000 dalton glycoprotein, which is associated with beta 2-microglobulin, the small subunit (12,000 daltons) of the HLA-A, -B, and -C antigens. The target antigen for the monoclonal reagent anti-T9 was found to be a glycoprotein of 94,000 daltons, which appears as a disulfide-linked dimer of 190,000 daltons on the cell surface. The antigen precipitated by the anti-T10 antibody is a 45,000 dalton glycoprotein. We present preliminary evidence that all three cell-surface proteins may be integral membrane proteins. These findings, in addition to the distribution patterns, suggest that the T6 antigen is the human homolog of the murine thymus leukemia (TL) antigen.

Antigens, Surface↗
PubMed1981

Deficiency of suppressor T cells in the hyperimmunoglobulin E syndrome.

The status of suppressor T cells (Ts) was assessed in seven children with the hyper IgE syndrome (recurrent staphylococcal infections, eczematous skin rash, and elevated serum IgE) to determine whether a deficiency in Ts is associated with increased IgE synthesis. When circulating T cells and their subsets were enumerated with the aid of monoclonal antibodies that identify T cells (T3), helper/inducer T cells (T4), and suppressor/cytotoxic T cells (T8), there was a selective deficiency of T3+ cells (51.7+/-11.2% vs. 66+/-5% for normal controls) and of T8+ cells (7.5+/-4.4% vs. 22+/-4% for normal controls) but not of T4+ cells (36.5+/-7.5% vs. 37+/-3% for normal controls). Suppressor T cell function was assessed by examining the ability of mononuclear cells incubated for 48 h with concanavalin A to suppress the proliferation of fresh autologous mononuclear cells in response to the mitogens phytohemagglutinin and pokeweed mitogen. All seven patients were severely deficient in concanavalin A-inducible suppressor cells. In vitro de novo synthesis of IgE in 6-d cultures of peripheral blood lymphocytes was measured in four patients by a solid-phase radioimmunoassay. Mononuclear cells from all four patients synthesized spontaneously increased quantities of IgE in vitro (4,950+/-3,760 pg/10(6) cells vs. 250+/-215 pg/10(6) cells for eight normal controls). IgE synthesis was suppressed by the addition of parental T cells to the culture. Elimination of the T8+ subset, but not of the T4+ subset, by complement-dependent lysis resulted in the loss of the capacity of parental T cells to suppress IgE synthesis. These results suggest that a deficiency of Ts underlies the elevated IgE levels observed in the hyper IgE syndrome.

Adult↗
PubMed1980

Biochemical analysis of human T lymphocyte differentiation antigens T4 and T5.

Two major functionally distinct T cell subsets in man have been defined with heteroantiserums and monoclonal antibodies directed against stable cell surface antigens that appear during thymic ontogeny. A monoclonal antibody to T4 antigen (anti-T4) is reactive with the peripheral inducer T cell population while a monoclonal antibody to T5 antigen (anti-T5) is reactive with the cytotoxic and suppressor population. Immunoprecipitation and electrophoresis on sodium dodecyl sulfate polyacrylamide gel were used to show that on human thymocytes or peripheral T cells the T4 antigen is a single 62,000-dalton glycoprotein while the T5 antigen is a complex of two glycoproteins, one being 30,000 daltons and the other 32,000 daltons. Similar glycoproteins have been isolated with antibodies to murine Lyt 1 and Lyt 2,3 antigens. Both the antigens defining the phenotypes of inducer and suppressor populations in man and mouse are structurally homologous.

Animals↗
PubMed1979

Acute graft-versus-host disease in recipients of bone-marrow transplants from identical twin donors.

Three patients with acute leukaemia received bone-marrow from identical twin donors after pre-transplant preparation with cyclophosphamide, cytosine arabinoside, and total body irradiation. Later clinical and microscopic changes in all three patients suggested cutaneous acute graft-versus host disease. In two of the recipients thrombolytic thrombocytopenia developed during the seventh week after transplantation, and platelet half-life was reduced to 9 h in one recipient (normal 3--4 days). It is suggested that acute graft-versus-host disease in bone-marrow recipients sometimes may result from an imbalance between autoreactive lymphocytes and lymphocytes which suppress their effect and not always from genetically determined histocompatibility differences between donor and recipient.

Acute Disease↗