Biomedical subjects

S R Burrows

Publications and source records attributed to S R Burrows.

79 records · Page 5Linked to original sources

PubMed1988

Cytotoxic T-cell clones discriminate between A- and B-type Epstein-Barr virus transformants.

Epstein-Barr virus (EBV) is the aetiological agent of infectious mononucleosis and is associated with Burkitt's lymphoma and nasopharyngeal carcinoma. The virus is harboured for life in all previously infected individuals and is apparently controlled by a population of EBV-specific memory T lymphocytes, specifically activated to recognize the functionally defined lymphocyte-detected membrane antigen. Two types (A and B) of EBV have been identified that show DNA sequence divergence within the BamH1 WYH region of the genome encoding the transformation-associated antigen, Epstein-Barr nuclear antigen 2 (EBNA 2) (ref. 4). To define the function of EBNA 2 in T-cell recognition, we have compared the ability of EBV-specific cytotoxic T-cell clones to distinguish between autologous B lymphocytes transformed by A- or B-type virus. We have now isolated both CD4 and CD8 cytotoxic T-cell clones that recognize autologous A-type but not B-type transformed lymphoblastoid cell lines, thus providing the first evidence that EBV-specific T-cell recognition can be mediated by EBNA 2. As this antigen is not expressed in Burkitt's lymphoma, this finding explains the failure of EBV-specific T-cell surveillance to eliminate the tumour.

B-Lymphocytes↗

PubMed1985

T lymphocytes in infectious mononucleosis. I. T cell death in vitro.

A large proportion of T lymphocytes isolated from the peripheral blood of acute infectious mononucleosis (IM) patients rapidly die when cultured in vitro, with greater than 50% dying within 12-15 h of seeding and up to 80% dying within 24 h. The cells die by apoptosis, a morphologically distinct mode of cell death that occurs in circumstances where death is a regulated event such as in embryonic development and hormone-dependent atrophy. In contrast, the level of cell death remained low in cultures of lymphocytes from controls and in the T cell depleted subpopulation from acute IM patients, with less than 2% and 10% of the lymphocytes dying by apoptosis after 36 h in culture, respectively. The rapid death of acute IM T cells in vitro does not involve soluble factors (including the serum fraction) or T cell to T cell contact. It is suggested that this observation may necessitate a re-evaluation of IM T cell function in vitro.

Cell Communication↗

PubMed1985

T lymphocytes in infectious mononucleosis. II. Response in vitro to interleukin-2 and establishment of T cell lines.

The addition of 20% interleukin-2 (IL-2) significantly reduced the percentage of T lymphocytes dying in vitro after being isolated from the peripheral blood of acute infectious mononucleosis (IM) patients. Moreover, the immediate addition of 20% IL-2 to freshly isolated blood allowed IM T cell lines to be readily established from the peripheral blood of acute IM patients. Characterization of seven of these IM T cell lines showed them to be T3+, T11+, T4-, T9- and generally T10-. Over half of the lines characterized were T8+. It will now be possible to re-evaluate IM T cell effector functions as previous assays of IM T cell functions may have been influenced by the presence of rapid and extensive T cell death in vitro.

Cell Line↗

PubMed1984

Calcium concentration defines two stages in transformation of lymphocytes by Epstein-Barr virus.

Lymphocytes from Epstein-Barr virus (EBV) seronegative donors were either stimulated with Protein A or infected with EBV and cultured in growth medium containing a range of calcium levels (700 microM to less than 2 microM available calcium). Three calcium end-points for the proliferation of B lymphocytes were defined: 18 microM for mitogenically-stimulated B cells; 8 microM for a pre-12 h event in EBV transformation and less than 2 microM for a post-12 h event in EBV transformation resembling the end-point for the emergent lymphoblastoid cell line. EBV-infected lymphocytes cultured in calcium-depleted medium expressed the EB virus nuclear antigen and proliferated after addition of calcium chloride. The present study should be useful both in defining the sequence of events in EBV transformation and in studying properties specific to the transformed phenotype.

Antigens, Viral↗

PubMed1983

Epstein-Barr virus specific T-cell response in nasopharyngeal carcinoma patients.

There is a substantial body of evidence suggesting an association between Epstein-Barr virus (EBV) and undifferentiated nasopharyngeal carcinoma (NPC). The present study has compared a group of NPC patients (newly diagnosed and long-term survivors) and controls for EBV-specific T-cell immunity using the regression of transformation assay. Newly diagnosed patients (17 tested) when compared with either long-term survivors (20 tested) or controls (30 tested) showed a significant impairment in virus-specific T-cell immunity (p = 0.036, p = 0.043 respectively). Furthermore, donors with IgA antibody to EBV showed a significant depression in virus-specific T-cell immunity compared with donors without IgA antibody (19 IgA-positive, 48 IgA-negative; p = 0.0025). These results may be important in explaining the postulated role of EBV in the aetiology of NPC.

Antibodies, Neoplasm↗

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↗

PubMedDate not supplied

Modification of the carboxyl terminal group affects replacement set analysis of a cytotoxic T cell epitope.

An Epstein-Barr virus-specific cytotoxic T cell (CTL) clone was previously shown to recognize the epitope FLRGRAYGL. The ability of substituted peptides to sensitize target cells for lysis by this clone was investigated using two peptide replacement sets, one synthesized with free carboxyl termini and another made with a carboxyl terminal beta-alanine-diketopiperazine (beta A-DKP) group. Curiously, the effect of certain substitutions differed for the two peptide sets. For example, NH2-FLRGRAYGL-beta A-DKP was 15-fold more active than NH2-FLRGRAYGI-beta A-DKR, but NH2-FLRGRAY-GL-COOH had the same activity as NH2-FLRGRAYGI-COOH. Evidence presented here illustrates that the activity of beta A-DKP peptide preparations was entirely due to contaminating peptides with free-COOH termini. The amount of active-COOH contaminants within a -beta A-DKP preparation thus appeared to vary depending on the substitution, resulting in some anomalous results from replacement set analysis using -beta A-DKP peptides.

Amino Acid Sequence↗