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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1506-1510
RAPID COMMUNICATION
Rapid Death of Adoptively Transferred T Cells in Acquired
Immunodeficiency Syndrome
Rusung Tan,
Xiaoning Xu,
Graham S. Ogg,
Pokrath Hansasuta,
Tao Dong,
Tim Rostron,
Graz Luzzi,
Christopher P. Conlon,
Gavin R. Screaton,
Andrew J. McMichael, and
Sarah Rowland-Jones
From Molecular Immunology Group, Institute of Molecular Medicine,
John Radcliffe Hospital, Oxford; Oxford Haemophilia Centre, Churchill
Hospital, Oxford; GUM, Wycombe General Hospital, High Wycombe; and
Infectious Diseases Unit, Churchill Hospital, Oxford, UK.
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.
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