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A M Krensky

Publications and source records attributed to A M Krensky.

At least 145 records · Page 8Linked to original sources
PubMed1984

Human lymphocyte function-associated antigens.

Three cell surface molecules, designated LFA-1, LFA-2, and LFA-3 were identified by mAbs selected for their ability to block cytolysis by an OKT4+, HLA-DR-specific CTL line. The LFA mAbs block all CTL and proliferative functions studied. In addition, anti-LFA-1 mAbs inhibit NK-mediated cytolysis. By analogy with murine LFA-1, human LFA-1 may be involved in the adhesion stage of cellular interactions. LFA-2, the SRBC receptor molecule, appears to be a T cell function-specific molecule. We have not yet established whether LFA-2 participates in antigen recognition or whether it is involved in antigen-non-specific interactions. The anti-LFA-3 mAb specifically blocks function by binding to the target cells, implying that LFA-3 may be a target ligand for an effector-specific receptor. The CTL-target interaction involves a number of steps, including antigen recognition, cell adhesion, and delivery of the lethal hit [22]. The LFA antigens show the complexity of this process at the molecular level. The anti-LFA monoclonal antibodies will be useful probes into the T cell immune response and may prove clinically relevant, both diagnostically and therapeutically.

Antibodies, Monoclonal↗
PubMed1984

Interactions of T lymphocytes with human vascular endothelial cells: role of endothelial cells surface antigens.

We have studied the interactions of peripheral blood T lymphocytes with cultured human vascular endothelial cells, focusing upon endothelial cell surface antigens important for T cell recognition. Under standard culture conditions endothelial cells express class I but not class II major histocompatibility complex (MHC) antigens. However, class II antigens may be induced by activated T cells or T cell products, including the lymphokine immune interferon. Immune interferon concomitantly increases class I antigen expression and causes a change in cell shape. In addition to vascular endothelial cells, we have found that vascular smooth muscle cells and human dermal fibroblasts may also be induced by immune interferon to express class II antigens. All known human class II antigens are induced (i.e. HLA-DR, DC and SB) as is the associated invariant chain. Induced antigen expression in these cells is stable over several days, although mRNA levels decline rapidly upon withdrawal of interferon. Vascular and stromal cell class II antigens are functional, in that they can be recognized by cytolytic and helper T cell clones. Several non-MHC antigens are also involved in the recognition of endothelial and stromal cells by T cells. We propose a model for the role of inducible class II molecules on endothelium and stromal cells in vivo: The induction of class II MHC antigens on endothelial cells, locally mediated by activated T cells, enables endothelium to present an immunogenic cell surface structure, comprised of antigen plus self class II polymorphic determinants, which in turn, serves to recruit additional antigen-specific T cells from the circulation into the site of a developing cell mediated immune response. Class II molecules on stromal cells, also induced locally at the site of a developing response, confers immune accessory function on these cells and may serve to augment and sustain a T cell response.

Antigen-Presenting Cells↗
PubMed1984

LFA-1, LFA-2, and LFA-3 antigens are involved in CTL-target conjugation.

Three cell surface antigens associated with the CTL-target cell interaction were previously identified by generation of mAb against OKT4+, HLA-DR-specific CTL, and selection for inhibition of cytolysis in a 51Cr-release assay. In this report, we showed that these mAb inhibit cytolysis by blocking CTL-target cell conjugate formation. It appears that LFA-1, LFA-2, and LFA-3 are cell surface structures involved in strengthening effector-target adhesion that accompanies antigen-specific recognition.

Antibodies, Monoclonal↗
PubMed1984

Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines.

A glycoprotein complex of 210,000 and 130,000 m.w., found on mitogen or alloantigen-stimulated human T cells and not on other hematopoietic cells, has been defined by a monoclonal antibody (Mab). The components of this complex are a subset of a larger family of proteins (210,000, 165,000 and 130,000 m.w.) defined by a second Mab. In a panel of hematopoietic cell lines and cell types, only activated T cells (including the cell line HUT-102) express the 210,000/130,000 complex and these cells also express the IL 2 receptor, a characteristic marker for activated T cells. The 210,000/130,000 m.w. complex (reactive with the Mab TS2/7) is present on all long-term activated T cells, including both the OKT4 and OKT8 subsets. The 210,000 m.w. subunit is expressed only on activated T cells. Other lymphoid cells express either the 130,000 m.w. subunit alone (unactivated lymphocytes, thymocytes, HUT-78) or the 130,000 subunit together with a 165,000 subunit (MOLT-4, HSB, and other leukemic T cell lines). The 210,000/130,000 m.w., 165,000/130,000 m.w. and 130,000 m.w. complexes are antigenically related in that all share reactivity with the Mab A- 1A5 . Among non-lymphoid hematopoietic cells and cell lines, none express the 210,000 m.w. chain; adherent cells (monocytes) and myeloid cell lines each express single proteins of 130,000 to 155,000 m.w. Granulocytes and red blood cells are negative and platelets express multiple bands (165,000 and 140,000 m.w.). Immunoperoxidase staining of tissue sections showed that a broad range of tissues and cell types had material cross-reactive with the lymphoid 130,000 m.w. protein. However, only a discrete subset of those tissues and cells including blood vessel walls, connective tissue, smooth muscle, kidney mesangial cells, and some non-cellular matrix tissue, had material cross-reactive with the 210,000 m.w. protein on activated T lymphocytes.

Animals↗
PubMed1984

Production of colony-stimulating factor(s) for granulocyte-macrophage and multipotential (granulocyte/erythroid/megakaryocyte/macrophage) hematopoietic progenitor cells (CFU-GEMM) by clonal lines of human IL-2-dependent T-lymphocytes.

Human T-lymphocyte lines that were selected for recognition of HLA-DR6 antigen and were dependent for growth in vitro on an added source of interleukin-2 (IL-2) were derived from the peripheral blood of normal individuals. Each was tested for production of a lymphokine(s) with properties of granulocyte-macrophage colony-stimulating factor (GM-CSF) using as target cells nonadherent cells from human long-term bone marrow cultures (LTBMC) or fresh marrow. Each of eight T-lymphocyte lines that were OKT3, OKT4, and HLA-DR positive produced GM-CSF that stimulated colony formation by both LTBMC cells and fresh marrow. Individually examined single-cell-derived bone marrow colonies growing in T-cell GM-CSF contained peroxidase-positive neutrophils, and macrophage-monocytes (GM-CFUc). Supernatant from a single-cell-derived T-cell clonal line designated F1 stimulated formation of granulocyte-macrophage colonies, megakaryocyte colonies, macroscopic erythroid bursts, and multipotential colonies containing erythroid cells, megakaryocytes, neutrophilic and eosinophilic granulocytes, and monocyte-macrophages (CFU-GEMM) in the presence of added erythropoietin. These data indicate that human IL-2-responsive T-lymphocytes produce lymphokine(s) that stimulate proliferation of primitive as well as committed hematopoietic stem cells, and implicate human T-lymphocytes in regulation of human multipotential hematopoietic stem cells in vivo.

Antigens, Surface↗
PubMed1984

Human cytolytic T lymphocyte interactions with vascular endothelium and fibroblasts: role of effector and target cell molecules.

Monoclonal antibodies (mAb) against cell surface structures have been used to identify several molecules involved in the interaction of human cytolytic T lymphocytes (CTL) with lymphoid and other bone marrow-derived targets. In allograft rejection or in graft-vs-host disease, however, major cellular targets are vascular and stromal cells, especially endothelium. Yet little is known about whether the same cell surface molecules are involved in the interactions of CTL with these cell types. We assessed the ability of mAb against effector or target cell structures to inhibit cytolysis of susceptible, cultured human vascular endothelium or dermal fibroblasts by a cloned human CTL line. Using mAb reactive with T3, T4, LFA-1, LFA-2, LFA-3, and HLA-DR, we found a qualitatively similar but quantitatively different pattern of inhibition of cytolysis as previously established for lymphoid targets by using the same CTL clone. These results have two implications: 1) the target cell structures recognized by CTL molecules such as T4, LFA-1 and LFA-2 are present on diverse cell types; and 2) the relative importance of such interactions may vary with target cell type. Furthermore, our studies provide several insights into the mechanisms of the interacting molecules. Our model system, and the use of pathophysiologically important target cells, may be useful for further analysis of CTL-mediated immune injury.

Antibodies, Monoclonal↗
PubMed1983

Tubulo-interstitial nephritis associated with polyomavirus (BK type) infection.

We studied viral injury to the kidney in a six-year-old boy with hyperimmunoglobulin M immunodeficiency who presented with irreversible acute renal failure and eventually died after five months of dialysis. Renal biopsy at the time of his presentation revealed a predominantly tubulo-interstitial process with numerous viral inclusions that were identified as polyomavirus. Urine cultures showed a massive viruria with BK-type, polyomavirus. The kidney disease was end stage, with persistence of BK virus identified by morphologic techniques and by culture. DNA hybridization analysis showed virus in low concentration in the lymph nodes, spleen, and lungs. The marked viruria, the high concentration of BK virus, and the extensive distribution of viral antigen throughout the kidney all suggest that infection with BK virus was the basis of the severe renal parenchymal injury.

Animals↗
PubMed1983

Epidemic and endemic HLA-B and DR associations in mucocutaneous lymph node syndrome.

HLA-A,B and DR antigens were evaluated in 51 patients with mucocutaneous lymph node syndrome (Kawasaki disease) during both endemic and epidemic periods in the Boston area. Although 80% of patients were HLA-B5 (70% HLA-Bw51) during endemic periods, there were no HLA-B5 individuals during the epidemic period. There was, however, an increased incidence of HLA-Bw44 during the Boston epidemic. Such different associations in endemic versus epidemic periods suggest possible different, as yet unknown, inciting agents.

Boston↗
PubMed1983

Human lymphocyte function associated antigen-1 (LFA-1): identification of multiple antigenic epitopes and their relationship to CTL-mediated cytotoxicity.

Human lymphocyte function-associated antigen (LFA)-1, a heterodimeric lymphocyte surface glycoprotein of 177,000 and 95,000 relative molecular weight has been implicated to function in the cytotoxic T lymphocyte (CTL) effector mechanism. Seven mouse hybridoma lines producing monoclonal antibodies (MAb) reactive with this structure were studied. Three unique and 3 partially over-lapping epitopes on human LFA-1 were defined by competitive cross inhibition binding assays using biosynthetically labeled anti-LFA-1 MAb. In contrast, of five rat antimouse LFA-1 MAb, all five recognized a common or shared epitope. An HLA-B7 specific human CTL line expressed 1.1 X 10(5) LFA-1 sites per cell with a direct saturation binding assay. Human CTL expressed two to four times more LFA-1 than peripheral blood lymphocytes or B and T lymphoblastoid cell lines. Titration of each of the anti-LFA-1 MAb in a 51chromium release cytolytic assay revealed quantitative differences in the ability of the different anti-LFA-1 MAb to block cytolysis indicating distinct functional and antigenic epitopes exist on the human LFA-1 molecule. Anti-LFA-1 MAb reversibly inhibited the CTL reaction by slowing the initial rate of cytolysis. These results suggest anti-LFA-1 MAb inhibit CTL function by specific blockade of a functionally relevant molecule.

Animals↗
PubMed1983

Cytotoxic T cells directed against HLA-DR antigens and their surface proteins.

The authors review their recent research involving the generation of cytotoxic T lymphocytes (CTL) directed against HLA-DR antigens. A mouse anti-human xenogeneic system first suggested that HLA-DR antigens could be recognized by CTL. Human allogeneic CTL specific for HLA-DR6 were generated and found to be OKT4+. The fact that these CTL were OKT4+ while anti HLA-A,B CTL were OKT8+ suggested that these T cell surface antigens may be involved in MHC antigen recognition; ie, they may be part of the T cell receptor. These OKT4+, HLA-DR specific CTL were further used to generate monoclonal antibodies (1) which block cytolysis and define novel antigens involved in the CTL-target interaction and (2) which define an antigenic complex on alloantigen activated T cells.

Animals↗
PubMed1983

The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: cell surface antigens associated with CTL-target interactions.

Three cell surface antigens associated with the cytolytic T lymphocyte(CTL)-target cell interaction were identified by generation of monoclonal antibodies (MAb) against OKT4+, HLA-DR-specific CTL and selection for inhibition of cytolysis in a 51Cr-release assay. These MAb block cytolysis by both OKT4+ and OKT8+ CTL and the proliferative responses to PHA and the mixed lymphocyte response (MLR). LFA-1 is an antigen widely distributed on lymphoid tissues and is composed of two polypeptides of 177,000 and 95,000 Mr on all cell types studied. Anti-LFA-1 MAb block NK cell-mediated cytolysis in addition to T lymphocyte-mediated cytotoxicity and proliferation. LFA-2 (Mr = 55,000 to 47,000), a determinant on the sheep red blood cell receptor, is expressed by T cells but not B cells and appears specific for T cell functions. LFA-3 (Mr = 60,000) is a widely distributed antigen present on both hematopoietic and nonhematopoietic tissues and appears to only be involved in T cell functions. MAb to LFA-1 and LFA-2 inhibit function by binding to effector cell surface molecules, whereas anti-LFA-3 MAb appear to block by binding to the target cells. Together with previously described molecules, LFA-1, LFA-2, and LFA-3 demonstrate the complexity of CTL-mediated cytotoxicity at the molecular level.

Antibodies, Monoclonal↗
PubMed1983

A DC-specific cytolytic T lymphocyte line is OKT8+1.

A human cytotoxic T lymphocyte (CTL) line, A9, was generated by limiting dilution and was selected because of its apparent DC specificity. A9 is 100% OKT3+, 90% OKT4+, and 10% OKT8+, but by negative selection the CTL present are entirely OKT8+. These OKT8+ CTL are totally inhibitable by Genox 3.53, an anti-DC1 monoclonal antibody (mAb), and Leu-10, an anti-DC subgroup mAb, but are not inhibitable by a panel of anti-HLA-DR mAb. These CTL are also inhibitable by anti-OKT3 and anti-LFA-2 but not by OKT4 or OKT8 mAb. These findings extend previous studies that showed that OKT8+ CTL recognize HLA-A,B antigens, whereas OKT4+ CTL recognize HLA-DR and SB antigens. It is possible that an as yet undefined T cell surface molecule is involved in DC recognition.

Antibodies, Monoclonal↗
PubMed1983

Causes of increased renal echogenicity in pediatric patients.

Review of 2,700 abdominal ultrasonic examinations revealed 56 patients whose kidneys showed increased echogenicity. Echogenic kidneys were associated with medical renal disease in 94% of cases (30% glomerular, 48% tubulointerstitial, 16% end-stage) and with no detectable renal disease in 6% (three patients). Patterns of increased echogenicity and renal size were evaluated. Specific patterns occurred in end-stage renal disease and polycystic kidney disease. Other medical renal diseases had overlapping ultrasonographic features. Some generalizations could be made although increased echogenicity was often nonspecific.

Child↗
PubMed1983

Hemolytic uremic syndrome and crescentic glomerulonephritis complicating childhood nephrosis.

Three children with nephrotic syndrome and focal segmental glomerulosclerosis and/or mesangial proliferation on renal biopsy developed the sudden onset of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. Two of the three children developed crescentic glomerulonephritis and never regained renal function while the third showed no change from his original histologic pattern and also developed chronic renal failure. These cases suggest an association between the lipoid nephrosis-focal segmental glomerulosclerosis group of glomerular diseases and crescentic glomerulonephritis, and may represent an unusual pathway in the evolution of childhood nephrosis.

Child↗
PubMed1982

Peritonitis in childhood nephrotic syndrome: 1970-1980.

A retrospective review (1970 through 1980) of 351 children with idiopathic nephrotic syndrome disclosed 24 episodes of peritonitis in 19 patients. Twenty-six percent of the patients had more than one episode. Streptococcus pneumoniae was the most common agent (50%), but Escherichia coli remained important (25%). Four cases (16%) were culture-negative. Signs of peritoneal irritation were present in all patients, including the 16 children receiving corticosteroid therapy. No morphological subtype of nephrotic syndrome could be demonstrated to be at increased risk for the development of peritonitis. Significantly decreased IgG levels and an apparent susceptibility to pneumococcal infection among blacks may be important risk factors.

Adolescent↗
PubMed1982

Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3.

Monoclonal antibodies were prepared to anti-HLA-DR cytolytic T lymphocytes (CTLs) and screened for inhibition of CTL-mediated killing. Binding of monoclonal antibodies to four types of molecules, LFA-1, LFA-2, LFA-3, and HLA-DR, inhibited killing, suggesting that these molecules participate in the CTL-target cell interaction. The antigens were characterized by immunoprecipitation, crosslinking, NaDodSO4/polyacrylamide gel electrophoresis, and immunofluorescence flow cytometry. The LFA-1 antigen contains alpha and beta polypeptide chains of Mr 177,000 and 95,000 that are noncovalently associated in an alpha 1 beta 1 structure. It is present on both B and T lymphocytes and marks subpopulations that differ in quantitative expression. Human LFA-1 appears to be the homologue of mouse LFA-1. Human LFA-2 is of Mr 49,000 with a minor component of Mr 36,000. It is expressed on CTL lines but not on a B-cell line and in peripheral blood preferentially on T lymphocytes. Human LFA-3 is of Mr 60,000 and is expressed on both B and T lymphocytes.

Animals↗