Ex vivo expansion of CD4 lymphocytes from human immunodeficiency virus type 1-infected persons in the presence of combination antiretroviral agents.
Expansion of CD4 lymphocytes from human immunodeficiency virus type 1 (HIV-1)-infected persons ex vivo has been limited by enhanced virus replication and cell death. The successful expansion of functional CD4 lymphocytes from HIV-1-infected persons has now been accomplished using a bispecific monoclonal antibody to CD3 and CD8 in combination with three antiretroviral agents. CD4 lymphocytes were polyclonally expanded by a factor of 10(3)-10(7) during 4-8 weeks in culture. Supernatants from most cultures were persistently HIV-1 p24 antigen-negative by day 14 and remained negative despite removal of antiretroviral agents at day 28. In such cultures, HIV-1 could not be recovered by cocultivation, and amounts of HIV-1 DNA declined or remained stable at low levels, eventually becoming undetectable in 2 cases. This approach establishes the feasibility of CD4 lymphocyte expansion in persons with HIV disease and may be useful for immune-based or gene therapies.
Wilson
C C
CC
Infectious Disease and Immunopathology Units, Massachusetts General Hospital, Boston 02114, USA.
Wong
J T
JT
Girard
D D
DD
Merrill
D P
DP
Dynan
M
M
An
D D
DD
Kalams
S A
SA
Johnson
R P
RP
Hirsch
M S
MS
D'Aquila
R T
RT
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D017931:DNA Primers; D004279:DNA, Viral / Q000097:blood*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D016325:HIV Long Terminal Repeat; D054303:HIV Reverse Transcriptase; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis
D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase