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Biomedical subjects

J H Pope

Publications and source records attributed to J H Pope.

At least 37 records · Page 2Linked to original sources
PubMed1986

Correlation between the presence of antibodies to the Epstein-Barr virus nuclear antigen type 2 and antibodies to the rheumatoid arthritis nuclear antigen in patients with rheumatoid arthritis.

The incidence of antibodies to Epstein-Barr nuclear antigen type 2 (EBNA-2) was determined in sera from rheumatoid arthritis (RA) patients and control subjects, by protein immunoblotting. Sixty-eight percent of the RA patients and 48% of the controls possessed anti-EBNA-2 antibodies. The titer of anti-rheumatoid arthritis nuclear antigen (RANA) in RA patient sera showed a stronger correlation with serum reactions to EBNA-2 than with reactions to EBNA-1. Our results indicate that the presence of EBNA-2 may make a major contribution to the RANA reaction.

Antibodies↗
PubMed1986

Reactions of sera from patients with rheumatoid arthritis, systemic lupus erythematosus and infectious mononucleosis to Epstein-Barr virus-induced polypeptides.

P3HR-1 and Ramos cells induced with sodium butyrate and 12-O-tetradecanoylphorbol 13-acetate were used in the protein immunoblot technique to identify Epstein-Barr virus (EBV)-specific antibodies present in sera from clinically normal individuals and patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and infectious mononucleosis (IM). Sixteen EBV-specific polypeptides were detected ranging in mol. wt. from 22,000 (22K) to 140K. Many of the sera contained antibodies to different subsets of these antigens, and a high proportion expressed autoantibodies which reacted with cellular components from an EBV genome-negative cell line. About 50% of the sera from each category reacted with the 44K to 48K and 36K and 38K early antigen (EA) components. A high proportion of the SLE sera (64%) were found to contain anti-EA antibodies, suggesting an association between EBV and SLE. Almost all of the EBV-seropositive sera examined contained antibodies against a 22K late antigen, but none of the sera from IM patients reacted with this polypeptide.

Antibodies, Viral↗
PubMed1986

Induction of Epstein-Barr virus nuclear antigens.

Lymphocytes were infected with the QIMR-WIL strain of Epstein-Barr virus, and the induction of Epstein-Barr virus-associated nuclear antigens was determined by using the protein immunoblot. There was a temporal increase in six antigens, with Epstein-Barr nuclear antigen 2 being detected 1 day after infection. The appearance of these antigens was shown to be independent of cellular DNA synthesis.

Antigens, Viral↗
PubMed1985

Inhibition of growth of certain human tumour cell lines by a factor derived from human fibroblast-like cell lines. I. Demonstration by mixed culture and by use of cell washings.

The growth of 7/9 Burkitt's lymphoma (BL) cell lines and 5/6 human melanoma cell lines was inhibited by certain human fibroblast-like cell lines, especially human myofibroblast cell lines. In contrast to BL lines, 3/5 lymphoblastoid cell lines were less susceptible and 3/4 human leukaemic lines were resistant. The effect was time- and concentration-dependent. Co-cultivation led to inhibition of tumour-cell growth within 3 days, but after removal from the fibroblasts, washing, and resuspending in fresh medium some tumour cells recovered and growth improved. The inhibitory activity was also demonstrated with washings of fibroblast-like cell lines, and was sensitive to pronase. The biological significance of this factor remains to be defined.

Autoradiography↗
PubMed1985

Identification of Epstein-Barr virus-induced polypeptides in P3HR-1 cells by protein immunoblot.

The protein immunoblot technique was used to identify Epstein-Barr virus-specific antigens present in sodium butyrate-induced P3HR-1 cells. Using sera from patients with either nasopharyngeal carcinoma or arthritis, 16 polypeptides were detected ranging in molecular weight from 22K to 140K. Each of the anti-EA-, anti-VCA-positive sera were found to contain antibodies to different subsets of the antigens. A 72K protein was identified which was consistent with the nuclear antigen (EBNA), and culturing cells in the presence of disodium phosphonoacetate allowed identification of 140K and 22K antigens as late viral products. Treatment of cells with sodium butyrate revealed that expression of some antigens increased in parallel with the time of incubation of the cells in butyrate while other antigens either appeared early and then decreased in intensity or were only present after a number of days of butyrate treatment. One of the antigens which decreased with the time cells were treated with butyrate was EBNA.

Antigens, Viral↗
PubMed1984

HLA-DR-antigen-associated restriction of EBV-specific cytotoxic T-cell colonies.

EBV-specific cytotoxic T cells can be generated in vitro in a secondary response. Several previous studies with bulk cultures provided evidence that cytotoxicity was restricted by HLA-A,B-related antigens. In the present family study, the EBV-specific cytotoxic T-cell response of a normal EBV-seropositive donor was analysed in detail by T-cell colony formation. Peripheral blood mononuclear cells were stimulated by the gamma-irradiated autologous lymphoblastoid cell line (LCL) and 3 days later seeded into agarose. Colonies were harvested, amplified by addition of interleukin-2 (IL-2), and analysed for T-cell markers and specificity in 51Cr-release assays. Twenty-two colonies were studied: all colonies were OKT3+, five were predominantly OKT4+, 9 were OKT8+ and 8 were mixtures. As expected from previous work, the OKT8+ colonies were cytotoxic for the autologous LCL target and cytotoxicity was blocked by monoclonal antibody (W6/32) to the nonpolymorphic determinants of HLA-A,B,C antigens. Significantly, the OKT4+ colonies tested also showed specific cytotoxicity, but lysis of the autologous LCL was blocked by the monoclonal antibody (OKlal) to the non-polymorphic determinants of HLA-DR antigens. Two interesting patterns of specificity were seen in cytotoxicity tests on sibling LCL targets. In one pattern, targets bearing the A11, B5, DR7 haplotype were lysed, while those bearing the A1, B8, DR3 were not, indicating haplotype preference. In the other pattern, there was lysis of the autologous cell line but not of the sibling targets. These results including HLA-DR-associated restriction, haplotype preference and strict self-preference, further illustrate the complexity of the EBV-cytotoxic T-cell response.

Adult↗
PubMed1984

Factors influencing the human cytotoxic T cell response to autologous lymphoblastoid cell lines in vitro.

Epstein-Barr virus (EBV)- and fetal calf serum (FCS)-specific cytotoxic human T cells can be generated in vitro, and have been shown to be HLA-antigen restricted. In the present work, peripheral blood mononuclear cells were stimulated with the gamma-irradiated autologous lymphoblastoid cell line (LCL) grown previously in FCS, human serum, or without serum. The induction and generation of cytotoxic T cells was carried out exclusively in culture medium containing autologous serum. With EBV-seronegative responders, FCS-grown stimulator LCL generated a FCS-specific cytotoxic T cell response. AB serum-grown LCL generated only a weak response, except at a high stimulatory dose, where the response tended to be essentially nonspecific. EBV-seropositive responders, in contrast, gave a typical secondary EBV-specific response regardless of the serum in which the LCL had been grown previously; no FCS response was detected. Dose-response and cold target inhibition studies confirmed these results. EBV immunity obviously plays a major role in the T cell response to the autologous LCL, which can no longer be viewed simply as a form of autologous mixed leucocyte reaction.

ABO Blood-Group System↗
PubMed1984

Identification of multiple Epstein-Barr virus-induced nuclear antigens with sera from patients with rheumatoid arthritis.

By means of the protein immunoblot technique, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) could be identified in a variety of EBV-transformed cell lines with anti-EBNA-positive sera from normal donors. The molecular weight of EBNA expressed in each of the cell lines varied between 70,000 and 75,000 and was dependent upon the strain of infecting virus. In contrast, 15 of 21 sera from patients with rheumatoid arthritis identified antigens in addition to EBNA. The most prominent of these antigens had molecular weights of 110,000 to 115,000 and 92,000. All of the EBV genome-positive cell lines except for QIMR-GOR and cell lines containing the P3HR-1 virus expressed these antigens. The antigens were not present in the EBV genome-negative Ramos and BJAB cell lines, nor were they identified with EBV seronegative sera, indicating that they were EBV related. There was no direct correlation between the presence of antibodies in sera to EBNA, viral capsid antigen or early antigen, and reaction with the 92,000-molecular-weight antigen in immunoblots, indicating that this antigen was distinct from previously described EBV-related antigens.

Animals↗
PubMed1983

A comparison of Epstein-Barr virus-specific T-cell immunity in malaria-endemic and -nonendemic regions of Papua New Guinea.

Epstein-Barr virus genome-positive Burkitt's lymphoma is endemic in Africa and Papua New Guinea and in both countries the tumour is restricted to regions with holoendemic malaria. The present work has compared groups of healthy indigenous individuals living in malarious and non-malarious regions of Papua New Guinea for Epstein-Barr virus-specific T-cell-mediated immunity using the in vitro regression assay. Residents of the malarious region (55 tested), when compared with either residents of the non-malarious area (35 tested) or Caucasian controls (27 tested) showed a significant (p less than 0.0001) impairment of virus-specific T-cell immunity but no obvious disturbance (p greater than 0.05) of anti-viral antibody titres. These results may be important in explaining the postulated role of malarial infection as a co-factor in the pathogenesis of Burkitt's lymphoma.

Adolescent↗
PubMed1982

Evidence for the involvement of HLA-DR antigens in restricted cytotoxicity by fetal calf serum-specific human T cells.

Fetal calf serum (FCS) generated at least two distinct populations of human cytotoxic cells in vitro. One population expressed natural killer (NK) cell-like activity and lysed K562 and HSB-2 targets more effectively than autologous or allogeneic lymphoblastoid cell lines (LCLs). The other population contained FCS-specific cytotoxic T cells which preferentially lysed the autologous LCLs and showed minimal lysis of K562. E-rosette separation and cold target competition experiments clearly established that NK cells were not involved in the self-reactive lysis. Moreover, the lytic activity of the E-rosetted T cells was reduced by up to 95% when autologous target cells were grown in human AB serum rather than FCS, showing that FCS-associated determinants on targets were essential in the cytolytic phase. Autologous LCLs grown in FCS were also considerably stronger competitors than human serum-grown LCLs. The consistent self-preferred lysis suggested that HLA antigen-related restriction was involved, but the patterns of lysis did not implicate HLA-A or B antigens, and monoclonal antibody (W6/32) to an A, B, and C monomorphic determinant failed to block FCS-specific lysis. In contrast, monoclonal antibody (DA.2) to a monomorphic determinant of DR effectively blocked FCS-specific lysis. Cytotoxicity tests with a small panel of DR-typed donors indicated that strong cross-reactions were invariably associated with sharing of DR antigens, particularly DR2, and to a lesser but significant extent DR7. Although DR antigen sharing did not always result in lysis of allogeneic targets, the overall evidence strongly suggests that FCS-specific T-cell cytotoxicity in humans is restricted by products encoded by or associated with the DR genes.

Animals↗
PubMed1981

Generation in vitro of EBV-induced specific cytotoxic T cells in autologous serum avoids complications due to self-preferred foetal calf serum-specific T-cell cytotoxicity.

A previous report has established that in cultures of human mononuclear leukocytes, foetal calf serum (FCS) is capable of generating high levels of T cells preferentially cytotoxic for the autologous lymphoblastoid cell line (LCL). The present study compared the capacity of Epstein-Barr virus (EBV) to generate cytotoxic T cells in cultures of mononuclear cells grown in FCS in this system. Five EBV-seropositive and three seronegative donors were used and cultures were harvested at 14 days. With cultures from seropositive donors, whether grown in FCS or in autologous serum, EBV infection generated T cells cytotoxic for the autologous LCL; the response in uninfected control cultures was markedly lower. With seronegative donor cultures grown in FCS, there was virtually no difference in the capacity of T cells generated in infected or uninfected cultures to lyse the autologous LCL. Moreover, cells from seronegative donors cultured in human serum gave no detectable lysis of autologous LCL in either infected or uninfected cultures, clearly showing the absence of a response to EBV. This evidence shows that it is possible to distinguish the generation of specific cytotoxic T cells by FCS from generation by EBV, and with certain donors the apparently EBV-induced response may actually include a significant component induced by FCS in the medium. The cytotoxicity patterns of EBV-induced and FCS-induced T cells for autologous and allogeneic LCL targets showed a degree of parallelism, stressing the need for caution in interpretation of data obtained from cultures using FCS.

Animals↗
PubMed1980

Long-term T-cell-mediated immunity to Epstein-Barr virus in man. IV. Development of T-cell memory in convalescent infectious mononucleosis patients.

Under appropriate culture conditions, EB virus infection of lymphocytes from seropositive donors leads to regression of transformation, and this was shown previously to be due to activation in a secondary immune response to T lymphocytes inhibitory for the autologous lymphoblastoid cell line. Regression can be quantified by determining the number of cells required for its expression. To investigate the development of memory T cells with EB-virus specificity in the primary infection, a comparison was made of the capacity for regression of lymphocytes from 16 cases of infectious mononucleosis (IM) and 13 normal donors. With 9 normal seropositive donors a mean lymphocyte concentration of 4.6 X 10(5)/ml was required to achieve 50% regression. In contrast, with 8 cases of IM tested within 1 week of onset, a much higher mean lymphocyte concentration (3.7 X 10(6)/ml) was necessary. Six of these IM cases, and another not tested in the first week, were tested on several occasions between 5 and 23 weeks after onset, and showed a slight reduction in the mean cell concentration required for regression (1.5 X 10(6)/ml). Six additional were tested 23--83 weeks after onset by which time the cell concentration required for 50% regression (mean = 4.5 X 10(5)/ml) had reached the level shown by normal seropositive donors. Regression did not occur with lymphocytes from seronegative donors, even at the highest cell concentration. Recombination cultures of T-cell-depleted and T-cell-enriched lymphocyte populations from 3 IM cases in ratios of 1:7 to 7:1 showed that the failure of regression in acute IM was not due simply to lack of sufficient numbers of T cells. The results indicate that EB-virus-specific memory T-cell activity as detected by the regression test is absent in the acute phase of IM, becomes evident at low levels 5--23 weeks after onset, and reaches a maximum after about 6 months.

Acute Disease↗
PubMed1980

HLA antigen-related restriction of T lymphocyte cytotoxicity to Epstein-Barr virus.

The specificity of cytotoxic T cells generated in Epstein-Barr virus (EBV)-infected lymphocyte cultures was investigated, using a 51Cr release assay. Potent cytotoxic T cells with preferred specificity directed to antigens expressed on autologous lymphoblastoid cell line (LCL) target cells were present in 14-day cultures of lymphocytes from EBV-seropositive donors and not from seronegative donors. Moreover, the cytotoxic patterns obtained with a panel of HLA antigen-related and unrelated LCL target cells, supported by unlabeled target inhibition tests, strongly indicate that T cell cytotoxicity to EBV is restricted to HLA antigens.

Antigens, Surface↗
PubMed1979

Long-term C-cell-mediated immunity to Epstein-Barr virus in man. II. Components necessary for regression in virus-infected leukocyte cultures.

Regression of EB-virus-induced transformation occurs exclusively in cultures of leukocytes from seropositive donors. Studies have shown that the strength of regression could be assayed in terms of the proportion of T cells which must be added to the autologous EB virus-infected T-cell-depleted population in order to establish regression in the culture. The in vitro regression phenomenon was strongly T-cell-dependent but did not require the presence of either monocytes or, as a potential antigenic stimulus, the residual viral envelope material on the surface of virus-infected B cells. The T-cell-depleted population from seropositive donors sometimes transformed (7/60 cultures) without the experimental addition of virus. Regression appeared to be independent of cytotoxic mechanisms involving anti-viral antibodies and not to be mediated by soluble factors released into culture medium.

Adult↗
PubMed1979

Long-term T-cell-mediated immunity to Epstein-Barr virus in man. III. Activation of cytotoxic T cells in virus-infected leukocyte cultures.

Experiments have been conducted to determine the role played by immune T cells in the regression of EB-virus-induced transformation which is exclusively seen in leukocyte cultures from sero-positive donors. Kinetic studies suggest that, in virus-infected cultures from such donors, a population of T cells proliferates within the first 2 weeks apparently in response to the appearance of virus-infected B cells. This proliferation continues to some extent during the period of regression. Nonspecific induction of T-cell proliferation by PHA did not induce regression in virus-infected cultures from seronegative donors and acutally prevented the regression in seropositive donor cultures. T cells harvested from seropositive donor cultures 11-14 days post infection were generally much more inhibitory to the growth of the autologous EB-virus-transformed cell line than were T cells either freshly prepared from whole blood or harvested from corresponding uninfected cultures; this inhibitory activity was either absent or much diminished when assayed against allogeneic target cell lines. The results suggest that virus-specific memory T cells capable of mounting a cytotoxic response when properly challenged in vitro.

Adult↗