Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller
Stephen A. Migueles, Cheryl Chairez, Siying Lin, Noah V. Gavil, Danielle M. Rosenthal, Milad Pooran, Ven Natarajan, Adam Rupert, Robin Dewar, Tauseef Rehman, Brad T. Sherman, Joseph Adelsberger, Susan F. Leitman, David Stroncek, Caryn G. Morse, Mark Connors, H. Clifford Lane, Joseph A. Kovacs
Stephen A. Migueles, Cheryl Chairez, Siying Lin, Noah V. Gavil, Danielle M. Rosenthal, Milad Pooran, Ven Natarajan, Adam Rupert, Robin Dewar, Tauseef Rehman, Brad T. Sherman, Joseph Adelsberger, Susan F. Leitman, David Stroncek, Caryn G. Morse, Mark Connors, H. Clifford Lane, Joseph A. Kovacs
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Clinical Research and Public Health AIDS/HIV Infectious disease

Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller

Abstract

BACKGROUND HIV-infected patients with poor virologic control and multidrug-resistant virus have limited therapeutic options. The current study was undertaken to evaluate the safety, immunologic effects, and antiviral activity of peripheral lymphocytes transferred from an elite controller, whose immune system is able to control viral replication without antiretroviral medications, to an HLA-B*2705–matched progressor.METHODS Approximately 22 billion cells were collected from an elite controller by lymphapheresis and infused within 6 hours into a recipient with a preinfusion CD4+ T cell count of 10 cells/μL (1%) and HIV plasma viral load of 114,993 copies/mL.RESULTS Donor cells were cleared from the recipient’s peripheral blood by day 8. A transient decrease in viral load to 58,421 (day 3) was followed by a rebound to 702,972 (day 6) before returning to baseline values by day 8. The decreased viral load was temporally associated with peak levels of donor T cells, including CD8+ T cells that had high levels of expression of Ki67, perforin, and granzyme B. Notably, recipient CD8+ T cells also showed increased expression of these markers, especially in HIV-specific tetramer–positive cells.CONCLUSION These results suggest that the adoptive transfer of lymphocytes from an HIV-infected elite controller to an HIV-infected patient with progressive disease may be able to perturb the immune system of the recipient in both positive and negative ways.TRIAL REGISTRATION ClinicalTrials.gov NCT00559416.FUNDING Intramural Research Programs of the US NIH Clinical Center and the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute.

Authors

Stephen A. Migueles, Cheryl Chairez, Siying Lin, Noah V. Gavil, Danielle M. Rosenthal, Milad Pooran, Ven Natarajan, Adam Rupert, Robin Dewar, Tauseef Rehman, Brad T. Sherman, Joseph Adelsberger, Susan F. Leitman, David Stroncek, Caryn G. Morse, Mark Connors, H. Clifford Lane, Joseph A. Kovacs

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Figure 7

Phenotype of donor and recipient CD4+ T cells changed after transfer, then reverted back to baseline.

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Phenotype of donor and recipient CD4+ T cells changed after transfer, th...
(A) Gated on CD4+ (CD8–) T cells, donor (HLA-A2–) cells (top row), which were primarily CCR7+CD27+ before transfer (left column), were predominantly CCR7–CD27– on day 1 before reverting to a CCR7+CD27+ phenotype by day 3 (right columns). In contrast, recipient (HLA-A2+) cells (bottom row), which were primarily CCR7–CD27+ before transfer (left column), were predominantly CCR7+CD27+ on day 1 before reversion to a CCR7–CD27+ phenotype (right columns). (B) Trends of recipient (blue symbols) and donor (red symbols) CCR7+CD27+CD4+ T cells over time. (C) Ki67 expression of gated recipient (blue symbols) and donor (red symbols) CD4+ (CD8–) T cells over time. In all panels, pretransfer donor results were derived from cells obtained from the donor; all other results were derived from cells obtained from the recipient before or after transfer.