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G Gillespie

Publications and source records attributed to G Gillespie.

At least 37 records · Page 2Linked to original sources
PubMed2001

What lies ahead.

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Chief Executive Officers, Hospital↗
PubMed2000

HLA class I-minor histocompatibility antigen tetramers select cytotoxic T cells with high avidity to the natural ligand.

INTRODUCTION: Cytotoxic T cells specific for the hematopoietic system-restricted minor histocompatibility antigens HA-1 and HA-2 are potential tools for the treatment of relapsed leukemia after minor histocompatibility antigen mismatched bone marrow transplantation. HA-1/HA-2-specific cytotoxic T cells with strong cytotoxic activity against HA-1/HA-2 positive target cells can be generated in vitro using HA-1 and HA-2 peptide-pulsed dendritic cells as antigen presenting cells. MATERIAL AND METHODS: We used HLA-A2 HA-1/HA-2 tetramers (HA-1(A2)/HA-2(A2) tetramers) to monitor the in vitro generation of HA-1- or HA-2-specific cytotoxic T cells. RESULTS: We show that the intensity of the tetramer-staining of the HA-1/HA-2-specific cytotoxic T cells strongly correlates with their capability to recognize mHag positive target cells. The bright tetramer-staining cytotoxic T cells lyse target cells expressing the natural ligand. The dim tetramer-staining cytotoxic T cells fail to lyse natural ligand positive target cells and lyse peptide-pulsed target cells only. The frequency of bright tetramer-staining, high avidity minor histocompatibility antigen-specific CTLs increases significantly upon appropriate antigen-specific restimulations. CONCLUSION: Our results demonstrate that HLA class I-minor histocompatibility antigen tetramers are useful tools for monitoring and selection of high avidity HA-1- and HA-2-specific cytotoxic T cells for adoptive immunotherapy.

Antigen Presentation↗
PubMed2000

High frequency of cytomegalovirus-specific cytotoxic T-effector cells in HLA-A*0201-positive subjects during multiple viral coinfections.

How the cellular immune response copes with diverse antigenic competition is poorly understood. Responses of virus-specific cytotoxic T lymphocytes (CTL) were examined longitudinally in an individual coinfected with human immunodeficiency virus type 1 (HIV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CTL responses to all 3 viruses were quantified by limiting dilution analysis and staining with HLA-A*0201 tetrameric complexes folded with HIV-1, EBV, and CMV peptides. A predominance of CMV-pp65-specific CTL was found, with a much lower frequency of CTL to HIV-1 Gag and Pol and to EBV-BMLF1 and LMP2. The high frequency of CMV-specific CTL, compared with HIV-1- and EBV-specific CTL, was confirmed in an additional 16 HLA-A*0201-positive virus-coinfected subjects. Therefore, the human immune system can mount CTL responses to multiple viral antigens simultaneously, albeit with different strengths.

Adult↗
PubMed2000

Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.

CD4(+) T cells are thought to be critical in the maintenance of virus-specific CD8(+) cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4(+) T-cell count decreases has been reported. Using HLA-peptide tetrameric complexes, we show the presence at high frequency of HIV-1- and cytomegalovirus-specific CD8(+) T cells when the peripheral CD4(+) T-cell count was low or zero in three HIV-1-infected patients. No direct virus-specific CD8(+)-mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitro in the presence of interleukin-2 into responsive effector cells. Thus, virus-specific CD8(+) T cells can be maintained in the peripheral circulation at high frequency in the absence of circulating peripheral CD4(+) T cells, but these cells may lack direct effector activity. Strategies designed to overcome this antigen unresponsiveness may be of value in therapies for the treatment of AIDS.

CD4-Positive T-Lymphocytes↗