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Adoptive transfer of syngeneic T cells in HIV‐1 discordant twins indicates rapid regulation of T‐cell homeostasis
Author(s) -
Hoffmann Christian,
Stellbrink HansJuergen,
Dielschneider Thomas,
Degen Olaf,
Stoehr Albrecht,
Knechten Heribert,
Wolf Eva,
Van Lunzen Jan
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06478.x
Subject(s) - cd8 , immunology , adoptive cell transfer , context (archaeology) , t cell , medicine , cytotoxic t cell , homeostasis , antigen , virology , immune system , biology , in vitro , paleontology , biochemistry
Summary The safety and efficacy of adoptive T‐cell transfer (ATT) was tested in the context of viral suppression in syngeneic twins discordant for human immunodeficiency virus type 1 (HIV‐1) infection. Human leucocyte antigen‐matched T cells of seven HIV‐negative twins were obtained by lymphapheresis and immediately transfused into the HIV‐infected sibling. Four twins received 12 ATTs each, with a mean of 2·10 ± 0·97 × 10 9 CD4 + T cells and 1·74 ± 0·81 × 10 9 CD8 + T cells. Additional transfers were performed in three more twin pairs to study the short‐term kinetics of transfused syngeneic T cells. Mean CD4 + T‐cell counts increased significantly, by 0·133 ± 0·136 × 10 9 cells/l at 1 h and 0·144 ± 0·12 × 10 9 cells/l at 3 h post‐transfusion ( P < 0·0001). Short‐term kinetic studies suggested a rapid clearance of transferred T cells from the peripheral blood within minutes due to a distribution to marginal pools. After a mean follow up of 39 months, however, a sustained increase of the mean CD4 + T‐cell count was observed (from 0·232 × 10 9 to 0·523 × 10 9 cells/l) without changes of plasma viraemia. We conclude that ATT combined with highly active antiretroviral therapy is safe and leads to a considerable increase in CD4 + T‐cell numbers. The clearance kinetics of the transfused cells from peripheral blood indicates a very rapid regulation of T‐cell homeostasis in HIV infection.