T cells are activated when the antigen-specific T cell receptor recognizes antigen in association with major histocompatibility complex (MHC) proteins. The T cell surface protein CD2 (T11, LFA-2, the T erythrocyte receptor) and its target or stimulator cell ligand, lymphocyte function-associated antigen-3 (LFA-3), are also involved in T cell adhesion and activation. The molecular mechanisms by which the CD2/LFA-3 interaction affects T cell adhesion and activation are unclear.
View Article and Find Full Text PDFThe lymphocyte cell surface molecule CD5 (T1, Leu 1, Tp67 in the human; Ly 1 in the mouse) is expressed on the majority of circulating T lymphocytes and a small population of B cells. We have analyzed CD5 expression on repopulating T cells in the peripheral blood of patients after allogeneic bone marrow transplantation (BMT). The frequency of CD3+ T cells that lack expression of CD5 is dramatically increased after BMT compared with the normal population.
View Article and Find Full Text PDFWhile the cellular sources for granulocyte-macrophage colony-stimulating factor (GM-CSF) are known to be widely distributed among several cell types, interleukin-3 (IL-3) gene expression has been demonstrated in only certain T-cell clones and in blood mononuclear cells stimulated with phytohemagglutinin (PHA) and phorbol-myristate-acetate (PMA). To determine which blood cells were responsible for this expression, we fractionated PHA/PMA-stimulated mononuclear cells and identified T lymphocytes as the source of IL-3 mRNA. Low-level IL-3 expression was detected as well in several stimulated human T-cell lines.
View Article and Find Full Text PDFCytotoxic T lymphocytes have been implicated as the effector cell mediating graft rejection following human allogeneic bone marrow transplantation. We have studied a BMT patient who rejected haploidentical T cell-depleted marrow. In vitro studies demonstrated that the circulating lymphocytes were CD3+ and CD8+, of recipient origin, and exhibited selective cytotoxicity against donor-specific class I major histocompatibility complex antigens.
View Article and Find Full Text PDFThe role of the CD5 surface molecule in T cell responsiveness to IL-1 was examined. A CD5-mutant Jurkat cell line was generated from a CD5+ parent cell line. This CD5- mutant subclone was infected with a defective retrovirus containing the CD5 cDNA and/or the neo gene encoding G418 resistance.
View Article and Find Full Text PDFThe addition of autologous erythrocytes to unfractionated human mononuclear cell cultures results in enhancement of B cell responses to antigens and mitogens. This costimulating effect of red cells is abrogated by their preincubation with anti-LFA-3 monoclonal antibody. Preincubation of mononuclear cells with anti-CD2 monoclonal antibodies (anti-Leu 5b, OKT11, used singly) has a down-regulating effect on B cell activation and no enhancement of B cell responses is seen when red cells are added to anti-CD2-treated cultures.
View Article and Find Full Text PDFT cells may be activated either by the antigen-specific T cell receptor (TCR)-CD3 complex or the cell surface receptor CD2. A natural ligand for CD2 has been found to be lymphocyte function-associated antigen 3 (LFA-3), a widely distributed cell surface glycoprotein. To investigate the interaction of these two pathways, we have expressed the cDNA encoding the human CD2 molecule in a murine T cell hybridoma that produces IL-2 in response to HLA-DR antigens.
View Article and Find Full Text PDFCell adhesion or conjugate formation between T lymphocytes and other cells is an important early step in the generation of the immune response. Although the antigen-specific T cell receptor confers antigen recognition and specificity, a number of other molecules expressed on the T cell surface are involved in the regulation of lymphocyte adhesion. T cell molecules that function to strengthen adhesion include lymphocyte function-associated antigen (LFA)-1, CD2, CD4, and CD8.
View Article and Find Full Text PDFRecently, it has been demonstrated that lymphocyte function-associated Ag (LFA-3) is a natural ligand for CD2 and that this receptor-ligand interaction functions in cell-cell adhesion. In this report, we demonstrate that LFA-3 plays a role in T cell activation. L cells were transfected with human genomic DNA and sorted for expression of LFA-3.
View Article and Find Full Text PDFIn order to define the function of the CD 5 (T1, Leu 1, Tp 67 in the human; Ly-1 in the mouse) molecule, a cDNA clone of human CD 5 was expressed in a CD5-deficient Jurkat cell line and in a murine T cell hybridoma. A Jurkat subclone (Jurkat 9.9) produced interleukin 2 (IL 2) in response to anti-CD 3 monoclonal antibody (mAb) cross-linked to solid support.
View Article and Find Full Text PDFAlthough the CD5 (T1) antigen was initially described as a pan-T cell membrane glycoprotein, we report that 14 of 40 normal individuals were found to have 5% or greater of their blood mononuclear cells characterized as CD3 (T3)+ but CD5- by dual immunofluorescence flow cytometry. These cells expressed normal quantities of surface CD3 and CD2 but low levels of CD7, were CD8+ and CD4-, and CD16-. In order to determine whether cells of this phenotype were functional, six CD5- cytolytic T lymphocyte (CTL) clones isolated from normal individuals were studied.
View Article and Find Full Text PDFTo define the role of the CD2-lymphocyte function-associated antigen 3 (LFA-3) interaction in T-cell activation, we have expressed a cDNA encoding the human CD2 molecule in a murine antigen-specific T-cell hybridoma. Expression of the CD2 molecule greatly enhances T-cell responsiveness to antigen; this enhancement is inhibited by anti-CD2 and anti-LFA-3 monoclonal antibodies (mAbs). CD2+ hybridomas produce interleukin 2 in response to combinations of anti-CD2 mAbs 9.
View Article and Find Full Text PDFWe have expressed the human CD4 and CD2 molecules in a murine hybridoma, 155.16, that responds to stimulation with human HLA-DR antigens by producing interleukin 2 (IL-2). When stimulated by HLA-DR expressing human cells, the CD4+ and CD2+ hybridomas produce significantly more IL-2 than the parent hybridomas, indicating that CD4 and CD2 are functional.
View Article and Find Full Text PDFWe have studied the lateral mobility of class 1 major histocompatibility complex (MHC) proteins in the membranes of human Epstein-Barr virus-transformed B cells using fluorescence photobleaching recovery. Class I MHC antigens were labeled with either W6/32 monoclonal antibody or its Fab fragment directly conjugated to fluorescein isothiocyanate. The diffusion coefficient of class I antigens labeled with Fab fragments of W6/32 was identical to that of a lipid analogue, fluorescein phosphatidylethanolamine, and was 10-fold greater than that of antigens labeled with intact W6/32.
View Article and Find Full Text PDFThe T-cell receptor (TCR) gamma gene product occurs in association with T3 (CD3) polypeptides on the surface of human T lymphocytes. TCR gamma lymphocytes express arrays of T3 polypeptides distinct from those typically observed on TCR alpha beta lymphocytes. This report demonstrates that identical T3 gamma, delta, and epsilon polypeptides are synthesized by TCR gamma lymphocytes and TCR alpha beta lymphocytes.
View Article and Find Full Text PDFThe mAb L10 was used to determine the distribution and the function of sialophorin, the heavily glycosylated surface molecule that is deficient/defective in lymphocytes of patients with the X-linked immunodeficiency Wiskott-Aldrich syndrome. Dual-parameter FACS analysis indicated that sialophorin is expressed on CD4+ and CD8+ lymphocytes, on a subpopulation of peripheral blood B lymphocytes, on all thymocytes, and on a subpopulation of bone marrow cells. Functional studies demonstrated that L10 mAb stimulates the proliferation of peripheral blood T lymphocytes as measured by stimulation of [3H]thymidine incorporation.
View Article and Find Full Text PDFThe involvement of the lymphocyte function-associated antigen-1 (LFA-1) membrane molecule in cytolytic T lymphocyte (CTL) interactions with lymphoid target cells was investigated using CTL clones derived from two patients with a heritable deficiency of LFA-1. LFA-1 surface expression on the CTL clones was 1% of the normal level of LFA-1, unchanged with prolonged culture, and identical on 14 different CTL clones. The function of the LFA-1 molecule was addressed using the LFA-1-deficient CTL clones and LFA-1-deficient lymphoid target cells.
View Article and Find Full Text PDFSecretion by tumor cells of circulating bone-resorbing factors may frequently underlie the hypercalcemia that occurs in patients with malignancy. Efforts to identify the responsible mediators have been hampered by a lack of available human tumor cell systems suitable for study of the pathogenesis of the humoral hypercalcemia syndrome. We have established a transitional-cell carcinoma (TCC) line in vitro from a patient with humoral hypercalcemia.
View Article and Find Full Text PDFTricyclic antidepressant drugs such as imipramine and desipramine have long been known to produce cardiovascular side effects including sinus tachycardia, prolongation of the P-R, QRS, and Q-T intervals, and decreased T-wave amplitude. Life-threatening ventricular ectopic activity has occurred after tricyclic drug overdose. Recently, maprotiline (Ludiomil), a tetracyclic anthracene-derivative antidepressant, has become available for the treatment of affective disorders.
View Article and Find Full Text PDFSince the rate of polymerization of sickle hemoglobin is exquisitely dependent on its concentration, a small reduction in intracellular hemoglobin concentration should cause a significant inhibition of sickling. In three patients with homozygous sickle cell anemia, sustained hyponatremia was induced by a program consisting of a high fluid intake, a low salt diet and a vasopressin analog, DDAVP. During periods of hyponatremia, mean corpuscular hemoglobin concentration (MCHC) fell 13% and in vitro sickling was reduced as assessed by morphology and oxygen affinity.
View Article and Find Full Text PDFBecause the formation of sickle cells is dependent on the intracellular concentration of deoxyhemoglobin S, we investigated the possibility of altering or preventing sickle-cell crises by reducing serum sodium so as to cause red cells to swell. In three patients with sickle-cell anemia who had been disabled by recurrent painful crises, sustained dilutional hyponatremia was induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in combination with a high fluid intake. Mean corpuscular hemoglobin concentration fell, and the degree of sickling at low partial oxygen pressure was reduced, as determined by morphologic criteria and by increased oxygen affinity of blood.
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