Papers by Sigbjørn Fossum
Immunobiology, 1984
Interdigitating cells: mononuclear phagocytes or dendritic cens? Interdigitating cells were first... more Interdigitating cells: mononuclear phagocytes or dendritic cens? Interdigitating cells were first described as a morphologically separate entity of cells in 1970 by VELDMAN (1). The most prominent features distinguishing IDC from typical macrophages were a highly irregular surface with numerous blunt, interdigitating protrusions, a strikingly pale peripheral cytoplasm owing to perinuclear packing of the organelles and a localization almost exclusively to thymus-dependent areas of lymphoid tissue. Veldman's observations were later confirmed and extended to other species (2, 3, 4) including man (5). However, despite many dissimilarities between IDC and typical macrophages IDC were considered to belong to the mononuclear phagocyte system (2, 3, 4, 6, 7, 8) and to acquire their peculiar morphology as a consequence of T-cell influence (3, 7). These considerations implied that IDC develop from monocytes seeded out from the bone marrow, which is a requirement for membership in the mononuclear phagocyte system (9, 10). Although IDC have been shown to originate from the bone marrow (11), proof of IDC development from monocytes is still lacking. The last point is crucial as IDC have also been included in a group of bone-marrow derived non-lymphoid cells (NLC) that are postulated to be separate from the mononuclear phagocyte system (rev. in 12). Among these are the dendritic cells (DC) isolated from mouse spleen (13) and rat lymph nodes (14), the Langerhans cells (LhC) of the skin (15) and the veiled cells (VC) of peripheral lymph (16), here collectively referred to as dendritic NLC. These cells differ from typical macrophages in several respects, most notably by possessing a highly irregular, veiled or dendritic, surface and by showing low phagocytic ability (17, 18, 19). In addition, whereas most typical macrophages do not express surface la-antigens unless stimulated by T cells (20, 21), the dendritic NLC are constitutively strongly Ia+ (22,23, 24,25,26). In accordance with current views about the pivotal role played by la-antigens in stimulation of helper T cells (rev. in 27) typical macrophages can be stimulatory, inert or suppressive when tested for antigen Abbreviations: IDC = interdigitating cells; DC = dendritic cells; VC = veiled cells; NLC = non-lymphoid cells; APC = antigen-presenting cells; ACC = accessory cells.
Journal of immunology (Baltimore, Md. : 1950), Apr 1, 2017
The functions of activating members of the killer cell Ig-like receptor (KIR) family are not full... more The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand-specific immunological synapses. HLA-C typing of target cells showed that KIR2DS2 recognition was independent of the HLA C1 or C2 group, whereas targets cells that were only recognized by KIR2DL3 expressed C1 group alleles. Anti-HLA class I Abs blocked KIR2DL3 responses toward C1-expressing targets, but they did not block KIR2DS2 recognition of cancer cells. Small interfering RNA knockdown of β2-microglobulin reduced the expression of class I H chain on the cancer targets by...
Scand J Immunol, 1980
Although lymph nodes are conventionally regarded as composed of superficial cortex, deep cortex, ... more Although lymph nodes are conventionally regarded as composed of superficial cortex, deep cortex, and medullary cords merge gradually into each other, the sinuses, the interstitium, and the germinal centres are separated by cellular borders that seem sufficiently complete to limit the rate of exchange of cells and molecules. Accordingly, the cellular composition shows distinct differences on either side of these borders. These compartments show further division into regions, the sinuses into superficial and deeply situated sinuses, the interstitium into superficial interstitium, follicles, paracortical nodules, and medullary interstitium, characterized by differences in densities of various cell types. Mechanisms behind the different distribution of cells within the different lymph node compartments and regions are discussed.
Eur J Immunol, 1991
We have previously shown that large granular lymphocyte (LGL)-enriched cell populations have the ... more We have previously shown that large granular lymphocyte (LGL)-enriched cell populations have the capacity to spontaneously recognize and kill allogeneic small lymphocytes and bone marrow cells (BMC) in vitro in certain strain combinations of rats. Here, we have studied the alloreactivity of natural killer (NK) cells from PVG nude (RT1c) rats against a panel of major histocompatibility complex (MHC) incompatible hemic cells. Both lymphocytes and BMC from the AO (RT1u), DA (RT1a), BN (RT1n) as well as the MHC-congenic PVG-RT1u (RT1u) rat strains were efficiently killed in vitro, whereas cells from syngeneic PVG rats were spared. The structures recognized on lymphocytes and BMC were probably similar since the two cell populations inhibited each other in cross-competition experiments. A number of features aligned the alloreactive effector cells with NK cells and not T cells. (a) Only about 5% of the effector cells from nude spleens expressed the T cell antigens CD3, CD5 or T cell receptor (TcR) alpha/beta whereas greater than 50% of the cells expressed markers present on NK cells (CD2, CD8, OX52 and the rat NK cell-specific marker NKR-P1 recognized by the monoclonal antibody 3.2.3). (b) The alloreactive cells were granular since pretreatment of nude spleen cells with the lysosomotropic agent L-leucine methyl ester which eliminated LGL, simultaneously abolished the cytolysis of both allogeneic lymphocytes and YAC-1 tumor cells. (c) Nude spleen cells stimulated with human recombinant interleukin 2 for 1 week in vitro generated large granular proliferating cells which were CD3-, CD5-, TcR alpha/beta-, but greater than 95% 3.2.3+. These cells efficiently killed allogeneic hemic cells from the same rat strains as did freshly isolated effector cells. (d) The cytolysis of allogeneic hemic cells could effectively be inhibited with unlabelled NK-sensitive (YAC-1 and K-562), but not NK-resistant (Roser leukemia) tumor cells. Cross-competition studies showed that PVG nude NK cells discriminated between AO, BN and DA BMC, suggesting that different alloantigens were positively recognized by subsets of NK cells. The mode of inheritance of the allodeterminant specifically recognized on AO BMC was investigated in crosses and backcrosses between AO and BN or DA rats. A gene dosage effect was observed in that this determinant was expressed at a slightly reduced level in F1 hybrids.(ABSTRACT TRUNCATED AT 250 WORDS)
Advances in Experimental Medicine and Biology, Feb 1, 1994
NK cells identify infected, neoplastic, or MHC-disparate target cells via several different recep... more NK cells identify infected, neoplastic, or MHC-disparate target cells via several different receptors. The NK cell receptor KLRE1 lacks known signaling motifs but has nevertheless been shown to regulate NK cell-mediated cytotoxicity. Here we demonstrate that KLRE1 forms functional heterodimers with either KLRI1 or KLRI2. Cotransfection with KLRE1 was necessary for surface expression of the NK cell receptor chains KLRI1 and KLRI2 in 293T cells. Moreover, KLRE1 can be coimmunoprecipitated with KLRI1 or KLRI2 from transfected NK cell lines. By flow cytometry, KLRE1 and KLRI1 showed colinear expression on NK cells, suggesting surface expression as heterodimers. Unlike other killer cell lectin-like receptors, KLRE1/KLRI1 and KLRE1/KLRI2 heterodimers predominantly migrated as single chains in SDS-PAGE, indicating noncovalent association. KLRI1 was coimmunoprecipitated with the tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1. In accordance with an inhibitory function, anti-HA Ab induced reduced killing of FcR-bearing targets by KLRI1-HA-transfected NK cell lines in a redirected cytotoxicity assay. Reciprocally, KLRI2-HA transfectants displayed increased killing in this assay. Finally, Ab to KLRE1 induced inhibition in KLRI1-transfected cells but increased cytotoxicity in KLRI2 transfectants, demonstrating that KLRE/I1 is a functional inhibitory heterodimer in NK cells, whereas KLRE/I2 is an activating heterodimeric receptor.
Tidsskrift for Den norske legeforening, 2015
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 10, 2002
Advances in experimental medicine and biology, 1988
Advances in experimental medicine and biology, 1988
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 28, 2007
Advances in Experimental Medicine and Biology, 1982
PLoS ONE, 2010
The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A s... more The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions.
Seminars in Immunology, 2008
Natural killer (NK) cells discriminate between normal syngeneic cells and infected, neoplastic or... more Natural killer (NK) cells discriminate between normal syngeneic cells and infected, neoplastic or MHCdisparate allogeneic cells. The reactivity of NK cells appears to be regulated by a balance between activating receptors that recognize non-self or altered self, and inhibitory receptors recognizing normal, self-encoded MHC class I molecules. Subfamilies of NK receptors undergo rapid evolution, and appear to co-evolve with the MHC. We here review present views on the evolution and function of NK cell receptors, with an emphasis on knowledge gained in cattle and rodents.
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Papers by Sigbjørn Fossum