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Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome
- Source :
- Europe PubMed Central
- Publication Year :
- 2016
-
Abstract
- Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>109) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor–specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.
- Subjects :
- Cytotoxicity, Immunologic
Male
Adoptive cell transfer
Receptors, Antigen, T-Cell, alpha-beta
Lymphocyte
T cell
Molecular Sequence Data
Immunology
HIV Infections
Biology
Biochemistry
Virus
medicine
Humans
Cytotoxic T cell
Amino Acid Sequence
Homosexuality, Male
Cell Death
Cell Biology
Hematology
Viral Load
Adoptive Transfer
Virology
CTL
medicine.anatomical_structure
HIV-1
Viral load
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Europe PubMed Central
- Accession number :
- edsair.doi.dedup.....3083ffaef1b846440fa7ad086e20ab6c