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F H Bach

Publications and source records attributed to F H Bach.

At least 253 records · Page 14Linked to original sources
PubMed1987

DQ beta sequences in HLA-DR4 haplotypes.

A cDNA clone encoding the entire mature DQ beta chain was isolated and sequenced from the DR4-Dw14 homozygous cell line, LS40. The sequence was compared with published DQ beta sequences from cells expressing DR4-DQw3, and found to be identical. The lack of DQ beta sequence polymorphism within this serotype (to date, DQ beta sequences have been derived from five cell lines comprising three Dw subtypes) adds to the data that suggest a recent evolutionary divergence of Dw subtypes within DR4-DQw3.

Base Sequence↗
PubMed1987

Protein analysis of HLA-DR2.3 haplotype.

The human major histocompatibility antigens (HLA-DR, HLA-DQ, and HLA-DP), consisting of alpha and beta chains, show extensive polymorphism. Based on differences of T-cell responses, the serologically defined DR2 specificity has been divided into Dw2, Dw12, and several putative additional "Dw subtype" specificities (AZH, FJO, and MN2, which we shall designate as "DR2.3", and LD-5a). To investigate the relationships of these specificities, DR and DQ molecules were analyzed by two-dimensional gel electrophoresis (2D-PAGE). The 2D-PAGE patterns of the DR molecules are identical among DR2.3 cells. Three DR beta chain polypeptides are expressed on DR2.3 cells. The electrophoretic mobilities of two of these beta chains are different from those of beta chains from the Dw2 and Dw12 cells. The DR molecules of the LD-5a cells show similar 2D-PAGE patterns with those of DR2.3 cells. The 2D-PAGE patterns of DQ molecules are identical among DR2.3 cells. The electrophoretic mobilities of DQ beta chains are different for Dw2, Dw12, LD-5a, and DR2.3 cells. These results indicate that the AZH, FJO, and MN2 cells have identical or very similar DR and DQ molecules and constitute a third, and relatively homogeneous, subgroup ("DR2.3") of the DR2 specificity. In addition, DR2.3 cells have a unique characteristic in that they express three DR beta chains.

Antibodies, Monoclonal↗
PubMed1987

Evolutionary and genetic implications of sequence variation in two nonallelic HLA-DR beta-chain cDNA sequences.

Most HLA haplotypes carry two expressed DR beta-chain genes; in the DR4 haplotype, the polymorphic locus has been called DR beta 1 and the apparently nonpolymorphic locus has been called DR beta 2. We have isolated nearly full-length DR beta-chain cDNA clones representing each of these two loci from a cell line homozygous for DR4 and Dw4. The clones have been sequenced and the sequences compared with published DR beta cDNA sequences derived from other haplotypes. A comparison of our sequences with other published cDNA sequences did not allow assignment of these other sequences to either the beta 1 or beta 2 locus. Comparison of our DR4 beta 1 sequence with DR beta 1 sequences isolated from other DR4-positive cells suggests that the alleles of DR4 beta 1 may have recently diverged from a common ancestor. The apparent lack of polymorphism of DR beta 2 may in part be a reflection of this recent divergence.

Alleles↗
PubMed1987

Cytotoxic T lymphocytes: blocked differentiation at the 'poised' stage.

The effect of different concentrations of phorbol myristate acetate (PMA) on the development of cytotoxic cells was studied. PMA was selectively able to prevent the development of cytotoxic cells in a mixed leucocyte culture, while allowing the responding cells to proliferate. The higher concentration of PMA (10(-5)M) blocked both direct cytotoxicity and lytic activity in the presence of lectin, while the lower concentration (10(-8) M) only prevented direct lytic function. The removal of PMA and subsequent addition of recombinant interleukin 2 (IL-2) or IL-2-containing supernatants effectively reversed the effect of PMA with recovery of antigen-specific lytic function of cells treated with 10(-8) M, while cells treated with 10(-5)M PMA only recovered lectin-dependent cytotoxic ability.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Long-term culture of LAK cells: expansion and activation signals.

Long-term culture of cells in rIL2-containing medium increases LAK activity on a per cell basis and produces an average 30-100-fold expansion over 14-21 days. The stimulation of PBL with anti-CD3 results in a 300-1000-fold increase in cell number while maintaining LAK activity. Cells stimulated with anti-CD3 and cultured in rIL2 for 12 days) can be further stimulated with beta IL1, or beta IFN, producing a further increase in LAK activity. These findings have allowed us to begin understanding the role of different signals in the activation of cells with LAK activity and together with biotechnological advances will allow for the culture of large numbers of cells for experimental and therapeutic purposes.

Antibodies, Monoclonal↗
PubMed1987

HLA associations with leukemia.

Frequencies of 35 HLA A, B, C, and DR antigens were determined in 1,834 leukemic Caucasoids to evaluate possible associations between HLA and leukemia. In comparison with the frequencies of HLA antigens in published controls, the frequency of Cw3 was significantly higher in patients with acute lymphoblastic leukemia (relative risk = 2.64, P less than 0.0002), acute myelogenous leukemia (relative risk = 1.92, P less than 0.0007), and chronic myelogenous leukemia (relative risk = 2.07, P less than 0.002; P values adjusted for multiple comparisons). The frequency of Cw4 was elevated in patients with acute lymphoblastic leukemia (relative risk = 2.01, P less than 0.0003), acute myelogenous leukemia (relative risk = 2.06, P less than 0.0002), and chronic myelogenous leukemia (relative risk = 2.14, P less than 0.0008). The frequency of Aw19 was significantly decreased in patients with acute myelogenous leukemia (relative risk = 0.68, P less than 0.01) and chronic myelogenous leukemia (relative risk = 0.59, P less than 0.005). None of the other 32 HLA antigens investigated had a statistically significant association with leukemia. The data suggest that Cw3 and Cw4 may be markers for leukemia susceptibility genes, while Aw19 may be a marker for decreased susceptibility to leukemia.

Adolescent↗
PubMed1987

Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation.

Successful adoptive cancer immunotherapy presumably depends on the accumulation of tumoricidal leukocytes at the sites of tumor growth. Large numbers of lymphokine-activated killer (LAK) cells can be generated in vitro by growth in high concentrations of interleukin-2 (IL-2), but relatively few arrive at the tumor site after intravenous injection. We hypothesize that the delivery of LAK cells to tumor sites may be augmented by previously demonstrated lymphocyte-recruiting factors, including activated macrophage products such as interleukin-1 (IL-1) and tumor necrosis factor. 111Indium-labeled LAK cells were injected intravenously into syngeneic mice bearing the macrophage activator endotoxin (LPS) in one hind footpad, and saline solution was injected into the contralateral footpad. Significantly more activity was recovered from the LPS-bearing footpad at all times during a 96-hour period. Recombinant IL-1 also attracted more LAK cells after injection into tumor-free hind footpads. Furthermore, LAK cells preferentially homed to hind footpads that were bearing 3-day established sarcomas after intralesional injections of LPS, IL-1, or tumor necrosis factor when compared with contralateral tumor-bearing footpads injected with saline solution alone. In preliminary experiments, mice with hind-footpad tumors appeared to survive longer after combined systemic IL-2 and LAK therapy if intralesional LPS was administered. These studies demonstrate that macrophage activation factors that have been shown capable of attracting circulating normal lymphocytes can also effectively attract LAK cells from the circulation. By the stimulation of macrophages at the sites of tumor growth, more LAK cells can be attracted. It is hoped that by "focusing" the migration of LAK cells to tumors, LAK cells and IL-2 would effect tumor regression more efficiently and with less toxicity.

Animals↗
PubMed1987

Lymphokine activated killer (LAK) cell-mediated endothelial injury: a mechanism for capillary leak syndrome in patients treated with LAK cells and interleukin-2.

We have investigated the possible etiology of a severe clinical syndrome seen in cancer patients treated with a new form of cancer-specific therapy, referred to as adoptive immunotherapy. This syndrome, apparently characterized by diffuse capillary injury, results in the leakage of intravascular fluid into interstitial tissues, with consequent organ dysfunction that limits the applicability of this form of therapy. We have demonstrated, using an in vitro model of cultured human endothelial cell injury, that LAK cells--lymphocytes stimulated in vitro by IL-2--appear to be potent mediators of endothelial injury. This LAK cell-mediated endothelial cytotoxicity is both time and dose dependent and is not manifested by freshly isolated human lymphocytes or lymphocytes cultured for up to 7 days in the absence of IL-2. In contrast, significant LAK cell-mediated damage to human endothelial cells is observed in lymphocytes cultured for as little as 24 hr in media containing IL-2 and is still found in 14-day-old LAK cells. LAK cells appear to be far more potent than maximally stimulated PMNs in their cytolytic activity against endothelium. In contrast, no damage to cultured endothelial cells is provoked by very large doses of IL-2 alone. Levels of IL-2 that are 3-5 times greater than peak blood IL-2 levels, transiently present in patients following bolus IL-2 injections, fail completely to produce HEC cytotoxicity even during prolonged incubation. The mechanism by which LAK cells kill their targets appears to be analogous to that previously described for related cytolytic T lymphocytes and NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillaries↗
PubMed1986

Depletion of donor Ia+ cells before transplantation does not prolong islet allograft survival.

Culture of pancreatic islets reduces their immunogenicity and results in prolonged graft survival after allotransplantation. The mechanism by which immunogenicity is reduced by culture is not known, but it has been suggested that prolonged graft survival is the result of the depletion of Ia+ cells from the graft. We studied the effect of eliminating Ia+ cells from islets before allotransplantation. Freshly isolated islets were incubated with anti-Ia serum plus complement or with monoclonal antibody to IAk plus complement or were left untreated before transplantation beneath the renal capsule of diabetic recipients. Incubation with anti-Ia serum plus complement eliminated intra-islet IA+ cells as demonstrated by indirect immunofluorescence staining. Incubation with monoclonal antibody to IAk plus complement significantly reduced but did not eliminate IA+ cells. Neither pretreatment regimen influenced survival of islet allografts placed beneath the renal capsule. However, untreated islets injected into the portal circulation were rejected in a low percentage of cases. We conclude that decreased immunogenicity observed after culture is not due solely to the depletion of Ia+ cells and that the site of engraftment has an important impact on graft survival.

Animals↗
PubMed1986

Interferon: a cytotoxic T lymphocyte differentiation signal.

Human T cell clones which were able to proliferate in response to specific stimuli but could not kill even in the presence of lectins were found to acquire the specific lytic function when interferon alpha or gamma was added on day 1 of the 7-day restimulation culture. These results demonstrate that interferon may act as a cytotoxic T lymphocyte differentiation signal. This signal can be blocked by the monoclonal antibody LeoA1 which recognizes a 70-kDa cell surface structure, involved in cytotoxic T lymphocyte differentiation.

Antibodies, Monoclonal↗
PubMed1986

DNA restriction fragment length polymorphisms characteristic for Dw subtypes of DR2.

DNA restriction fragment length polymorphisms (RFLP) can be easily demonstrated in DNA of cells expressing different DR specificities when class II cDNA probes are used for hybridization. Previous studies of DR4+ homozygous typing cells (HTCs) carrying different Dw subtypes, however, detected no RFLP correlating with subtypes. In contrast, we report here Southern blotting studies of DR2+ HTCs carrying different subtypes which showed RFLP patterns characteristic for each subtype, using both DR beta and DQ beta probes and several restriction enzymes. The RFLP between subtypes of DR2 was, however, appreciably lower than that found between DR specificities.

DNA↗
PubMed1986

NO1: an HLA-DQw1-associated determinant present on loss mutants not expressing DQw1.

We have used two monoclonal antibodies, FA and Tu39, and cloned cytotoxic T lymphocytes to study the immunogenetic control of an HLA-D region-encoded determinant(s) recognized by the Tc other than class I or DR or DQ. The Tc recognize a determinant associated with one (the A2) haplotype of LCL721 and are lytic to mutants of LCL 721 that have lost expression of all class I as well as the serologically defined DR and DQw specificities associated with, and presumably identical to, DPw2, the specificity encoded by the sensitizing (A2-B51) haplotype; these data provide the first evidence that FA recognizes the protein dimer presumably expressing the DPw determinant. Those Tc blocked by Tu39 recognized a determinant, referred to as NO1, that is not associated in the population with DPw2, but is found on some, but not all, DQw1-positive cells. We propose three possible explanations for these results. (i) There may be a class II product other than DP or those expressing the DR or DQ serologically defined specificities carrying NO1; such a product could be either as yet undescribed (E. Long has obtained information for an expressed and as yet undefined class II beta gene, personal communication) or a second expressed dimer of the DQ or DP families. (We assume that no DR genes of the A2 haplotype are expressed in these mutants. (ii) NO1 and DPw2 may be on the same molecule; to account for the lack of association of NO1 and DPw2 in the population, one might propose a mechanism such as gene conversion leading to expression of NO1.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗