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Biomedical subjects

A F Geczy

Publications and source records attributed to A F Geczy.

At least 37 records · Page 2Linked to original sources
PubMed1993

Peptide sequences with strong stimulatory activity for lymphoid cells: implications for vaccine development.

Seven peptides derived from the bacterial major outer-membrane protein TraT were synthesized and then tested in lymphoproliferative assays using lymphoid cells from a variety of animals that had been immunized with the native TraT molecule in saline. A hierarchical pattern of responsiveness to the peptides was observed in the four animal species studied and in particular three of the peptides (T2, T4 and T6) showed very strong responses in all species. The 'universality' of the TraT-derived peptides was confirmed by studying the responsiveness of lymphoid cells obtained from the peripheral blood of twenty clinically normal human donors. Thus, following a secondary in vitro immunization with TraT-pulsed human peripheral blood mononuclear cells, responsiveness to TraT and to the TraT-derived peptides was observed in the cultures derived from all twenty donors. Taken together, our findings imply that the putative T-cell epitope peptides (T2, T4 and T6) could be employed as carriers in subunit vaccines and thereby help to overcome the unresponsiveness observed in animals and humans as a result of MHC restriction.

Adjuvants, Immunologic↗
PubMed1993

Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent.

OBJECTIVE: To evaluate the potential of TraT to restore HIV-specific cell-mediated immunity. DESIGN: CD4+ T cell-associated antiviral and recall antigen-specific lymphoproliferative responses are generally impaired or absent in HIV-infected individuals. METHODS: Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and symptomatic HIV-infected individuals, we compared the immunomodulatory effects of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. RESULTS: Exogenous IL-2 enhanced lymphoproliferation induced by an immunodominant synthetic HIV gp41 analogue, gp41[8] (amino acids 593-604), in four out of 10 asymptomatics and six out of 19 symptomatics. In contrast, TraT acted synergistically with gp41[8] to augment HIV-specific proliferation with higher frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV-infected individuals, irrespective of CD4+ T-cell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex-restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other less immunodominant HIV analogues. CONCLUSIONS: These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected individuals, as well as cellular immune functions in individuals suffering from other immunodeficiency disorders.

Adjuvants, Immunologic↗
PubMed1988

Cross-reacting bacterial determinants in ankylosing spondylitis.

The importance of the association between the human histocompatibility antigen human leukocyte antigen-B27 and ankylosing spondylitis is undisputed, but its biologic significance remains unresolved. We have demonstrated specific cross reactivity between a range of enteric bacteria and a specific determinant found only on the surfaces of cells from human leukocyte antigen-B27-positive persons with ankylosing spondylitis. We have proposed that the genetic element coding for this cross-reactive determinant is mobile and that its acquisition by B27-positive cells in vivo represents an important step in the eventual development of ankylosing spondylitis.

Antigens, Bacterial↗
PubMed1987

An antiserum to a disease-associated factor from the cells of an HLA-B27 positive patient with ankylosing spondylitis specifically recognizes an HLA-B27 associated determinant.

Antiserum raised to a factor elaborated by a lymphoblastoid cell line derived from the peripheral blood cells of an HLA-B27 positive patient with ankylosing spondylitis specifically lyses the B27 positive, but not the B27 negative, cells of ankylosing spondylitis patients. The cells of B27 positive and B27 negative normal controls are not lysed. This serum has similar specificity to antisera against cross-reactive bacteria.

Cell Line↗
PubMed1986

Cytotoxic T lymphocytes against disease-associated determinant(s) in ankylosing spondylitis.

Cytotoxic T lymphocytes, induced by stimulating the PBMC of an HLA-B27+ normal individual (B27+, AS-) with the PBMC of an HLA-identical sibling suffering from ankylosing spondylitis (AS) (B27+, AS+), specifically lyse B27+, AS+ PBMC but not PBMC from HLA-27+ or B27-, AS- normal controls, or from HLA-B27- AS patients (B27-,AS+). CTL of similar specificity can also be raised by immunizing in vitro B27+,AS- cells with autologous cells modified by cross-reactive bacterial antigens. These results suggest that CTL can recognize certain bacterial antigens in association with HLA-B27 and that this interaction may lead to an inflammatory episode during the initial stages of the disease.

Escherichia coli↗
PubMed1986

Biochemical studies on a factor isolated from Klebsiella K43-BTS1 that cross-reacts with cells from HLA-B27 positive patients with ankylosing spondylitis.

A component of the cell walls of certain enteric bacteria has been identified that cross-reacts with an HLA-B27-associated cell-surface structure on lymphocytes and other cell types from patients with ankylosing spondylitis. This component, or "modifying factor," from one particular organism, Klebsiella K43-BTS1, has been studied in detail. A purification scheme has been developed using preparative electrofocusing and gel-permeation high performance liquid chromatography techniques and the purified material used in various characterization studies. A previous study demonstrated that the modifying factor has an approximate molecular weight of 30,000 and an isoelectric point of 5.4-5.5. In this study two-dimensional gel electrophoresis experiments demonstrated that the modifying factor is associated with a single protein component of the cell wall of this organism. Pronase and papain destroyed the modifying factor activity whereas trypsin and alpha-chymotrypsin degraded the factor into smaller fragments without destroying its ability to modify B27+ AS- lymphocytes. Neuraminidase did not affect the modifying factor itself but did affect B27+ AS- lymphocytes such that they became unresponsive to modification. Sugar inhibition studies suggested that sugar groups are probably not involved in the function of the modifying factor. The availability of purified modifying factor should permit more detailed chemical analyses as well as functional studies to determine the significance of this molecule to the pathogenesis of ankylosing spondylitis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Blind confirmation in Leiden of Geczy factor on the cells of Dutch patients with ankylosing spondylitis.

A follow-up blind study, of the ability of "cross-reactive" antisera to distinguish between the cells of Dutch patients with ankylosing spondylitis (AS) and normal controls, was performed in Leiden. Of the 45 cell samples tested, 29 were fresh peripheral blood mononuclear (PBM) cells while 15 were cryopreserved PBM. No false positives but one false negative was identified among the 45 samples, and the "negative" was confirmed after the recoded cryopreserved cells from this patient were retested. It is concluded that the "cross-reactive" antisera raised in Sydney give good discrimination between patients and normals. Factors affecting the success of the 51Cr-release cytotoxicity assay, and possible reasons for the failure of others to confirm these observations, are briefly discussed.

Antigens, Surface↗
PubMed1986

HLA-B27 associated cross-reactive marker on the cells of New Zealand patients with ankylosing spondylitis.

We have previously shown that antibodies raised in rabbits to certain enteric bacteria will specifically lyse, in a 51Cr release assay, the peripheral blood lymphocytes (PBL) of 80% of HLA-B27 positive patients with ankylosing spondylitis (B27+ AS+) but not the PBL of HLA-B27 positive normal controls (B27+ AS-). Other laboratories have been unable to reproduce these findings. This study was designed to ascertain whether this lack of reproducibility was due to a peculiarity of our B27+ AS+ patients or to technical difficulties in the complement mediated 51Cr release assay. We have shown in this blind study that the PBL of 16 out of 18 B27+ AS+ patients from a New Zealand population were lysed by our antisera but none of the PBL of 20 B27+ AS- normal controls were lysed. The phenomenon of 'cross reactivity' between certain enteric bacteria and B27+ AS+ PBL is not confined to the Sydney AS population.

Adult↗
PubMed1986

Significance of non-pathogenic cross reactive bowel flora in patients with ankylosing spondylitis.

We have previously shown that antisera raised in rabbits to certain enteric cross reactive strains of bacteria are capable of specifically lysing the peripheral blood lymphocytes of HLA-B27 positive patients with ankylosing spondylitis (B27+ AS+). We now report that bacteria with cross reactive antigenic determinants are found in the bowel flora of all of 52 B27+ AS+ patients but in only one of 50 HLA-B27 positive normal controls (B27+ AS-). These organisms are functionally similar to the cross reactive enteric bacteria originally reported. They are not confined to a particular genus or species and their cross reactive serological nature appears to be a property shared by all enteric organisms isolated from B27+ AS+ patients. Organisms with these properties have been shown to persist in the bowel flora of 14 B27+ AS+ patients followed up for more than one year.

Adult↗
PubMed1985

The modification of HLA-B27-positive lymphocytes by the culture filtrate of Klebsiella K43 BTS 1 is a metabolically active process.

The culture filtrate of some bacteria contains a modifying factor which specifically interacts with the cells of HLA-B27-positive normal individuals (BS+ AS-); this modification results in a serologically detectable change similar to that seen on the cells of patients with ankylosing spondylitis (B27+ AS+). Puromycin, 5-azacytidine, actinomycin D, cyclosporin A, dexamethasone, indomethacin, colchicine, quinacrine, chlorpromazine but not tunicamycin can effectively inhibit the in vitro modification of HLA-B27-positive lymphocytes from normal individuals. These studies suggest that a number of different metabolic pathways may be involved in the modification of B27+ AS- lymphocytes by certain enteric antigens.

Antigens, Bacterial↗