The growth response to tumour necrosis factor alpha of human gynaecological cancer cell lines.

The cytokine tumour necrosis factor alpha (TNF-alpha) is implicated in the regulation of diverse gynaecological cell types, its biological activity being potentially mediated by two distinct cell surface receptors (TNFR) of molecular weight 55 and 75 kDa, respectively. In this study the sensitivity to the growth regulatory properties of TNF-alpha of a panel of human cervical, endometrial and ovarian cancer cell lines was investigated in relation to the expression and biological activity of the 55- and 75-kDa receptor. There was no evidence of expression or function of the 75-kDa receptor in any of the cell lines tested.

Maturation of Qa-1b class I molecules requires beta 2-microglobulin but is TAP independent.

Two conformationally distinct and stable forms of Qa-1b, one strongly associated with beta 2-microglobulin (beta 2m) and the other associated with a novel molecule, gp44, were observed during immunochemical studies on the expression of Qa-1b molecules in mouse spleen cells. Both forms are efficiently processed and expressed at the cell surface. However, a large proportion of Qa-1b was found to be disulfide linked to gp44 without any detectable beta 2m.

Qa-1 interaction and T cell recognition of the Qa-1 determinant modifier peptide.

The peptide-binding properties of the nonclassical major histocompatibility complex (MHC) class 1b molecule Qa-1 were investigated using a transfected hybrid molecule composed of the alpha 1 and alpha 2 domains of Qa-1b and the alpha 3 domain of H-2Db. This allowed the use of a monoclonal antibody directed against H-2Db whilst retaining the peptide-binding groove of Qa-1b. By comparison with classical MHC class I molecules, intracellular maturation of the chimeric molecule was inefficient with weak intracellular association with beta 2-microglobulin.

CD4 expression on dendritic cells and their infection by human immunodeficiency virus.

Infection of dendritic cells (DC) by human immunodeficiency virus (HIV) has been disputed. Employing a fluorescence-activated cell sorter, DC, identified by the absence of membrane markers for T, B, natural killer (NK) and monocytic cells and by high levels of MHC class II DR antigen, were shown to express low levels of CD4. Immunomagnetic beads were used to separate blood low density cells, which are enriched for DC, into CD4-positive and -negative populations.

Synergistic interactions of CD4+ and CD8+ T cell subsets with human vascular endothelial cells in primary proliferative allogeneic responses.

The ability of subcultured human vascular endothelial cells (EC) to provide immune accessory functions for proliferative responses of highly purified allogeneic CD4+ and CD8+ T cells has been examined. CD4+ T cells proliferated in response to IFN-gamma-pretreated EC which expressed class II molecules, but not to untreated EC. CD8+ T cells proliferated to MHC class I molecules expressed on both untreated and IFN-gamma-treated EC.

Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow.

Colonies of CD1a+ HLA-DR+/DQ+ CD4+ cells with the functional and some of the structural attributes of Langerhans cells are observed in human bone marrow cultures in semi-solid media and are assumed to be the progeny of an early progenitor, the dendritic/Langerhans cell CFU (CFU-DL). The cytokine-regulated growth of these cells has been studied using a chemically defined serum-free system to culture both unfractionated and highly enriched bone marrow progenitor cell populations. Although unfractionated cell growth was optimal in serum replete cultures with PHA-stimulated leukocyte-conditioned medium (PHA-LCM) suboptimal proliferation of CFU-DL was observed in serum even in the absence of PHA-LCM.

Function of dendritic cells and changes in T cell proliferation in antigen-induced nonresponsiveness.

The ability of dendritic cells (DC) to acquire and present antigen to T cells during antigen-induced nonresponsiveness (AINR) in contact sensitivity was examined by studying cells from lymph nodes draining the sites of antigen challenge. Mice were pretreated on the right flank with either vehicle (AOO), oxazolone (Ox), or fluorescein isothiocyanate (FITC) and challenged 5, 10, or 20 days later with FITC on the left flank. At 5, 10, and 20 days, compared with animals pretreated with vehicle and challenged with FITC, those pretreated and challenged with FITC showed reduced acquisition of antigen by DC and the DC showed a reduced ability to stimulate naive T cells in vitro.

LFA-1-dependent OKT3-driven T cell clusters in common variable immunodeficiency.

The triggering of the TCR/CD3 complex by anti-CD3 (OKT3) antibody leads to the formation of T cell clusters. In cultures of T lymphocytes from most normal individuals, the peak of cluster formation occurs at 24 h, but with cells from patients with common variable immunodeficiency (CVI) it was seen earlier at 4-9 h; in addition, the clusters were larger than normal, particularly at 9 h. Cluster formation by CVI and normal cells was dependent on temperature and divalent cations, but did not require Fc receptors.

Nutrition and immunity: the immunoregulatory effect of n-6 essential fatty acids is mediated through prostaglandin E.

Suppression of cell-mediated immune responses by essential fatty acids (EFA) was demonstrated in mice maintained on a standard laboratory diet for rodents. Daily oral administration of EFA at doses ranging from 125 to 750 mg/kg body weight significantly suppressed local host-versus-graft and graft-versus-host reactions as measured by popliteal lymph node assay. Studies employing immune sera directed against E-type prostaglandin demonstrated that n-6 EFA-induced suppression was mediated through prostaglandin E1.

Prostaglandins and cell-mediated immunity. The role of prostaglandin E1 in the induction of host-versus-graft and graft-versus-host reactions in mice.

Based on studies in lymphocyte cultures it has been suggested that endogenous prostaglandins (PG), especially those of the E series (PGE), suppress cell-mediated immune reactions during their induction phase. We have tested this theory in experimental animals using local host-versus-graft (HVG) and graft-versus-host (GVH) reactions in mice. These reactions were suppressed in a dose-dependent manner by treatment of the animals with PGE1.

Induction of immune responses in vivo with small numbers of veiled (dendritic) cells.

The role of dendritic or veiled cells (VC) from lymph nodes or spleens of rats and mice in initiating immune responses in vivo has been investigated. Host-versus-graft responses were induced by injection of VC from spleens of (C57BL/10 X CBA) F1 mice into the footpads of parental strain (CBA) animals and measured by the increase in the weight of the draining popliteal lymph nodes. The potency of VC to induce the responses was 100-fold greater than that of unseparated spleen cells.

The spleen is required for the suppression of experimental allergic encephalomyelitis by prostaglandin precursors.

In this paper we report a study of the effects of splenectomy on the immunosuppressive action of essential fatty acids (EFA) which is thought to be mediated through prostaglandins (PG) produced in the spleen. Experimental allergic encephalomyelitis (EAE) was induced in normal, splenectomized and sham splenectomized Lewis rats. EFA were administered orally, the animals in the control groups being treated with liquid paraffin.

Suppression by essential fatty acids of experimental allergic encephalomyelitis is abolished by indomethacin.

Experimental allergic encephalomyelitis in Lewis rats was suppressed by treatment with essential fatty acids (EFA) given perorally. This treatment effect could be abolished by administration of a drug (Indomethacin) known to inhibit biosynthesis of certain prostaglandins from EFA. This observation suggests that the suppressive effect of EFA on cell-mediated immune reactions is brought about by EFA-derived prostaglandins.