Ex vivo expansion of CD4 lymphocytes from human immunodeficiency virus type 1-infected persons in the presence of combination antiretroviral agents

C C Wilson; J T Wong; D D Girard; D P Merrill; M Dynan; D D An; S A Kalams; R P Johnson; M S Hirsch; R T D'Aquila

doi:10.1093/infdis/172.1.88

Ex vivo expansion of CD4 lymphocytes from human immunodeficiency virus type 1-infected persons in the presence of combination antiretroviral agents

J Infect Dis. 1995 Jul;172(1):88-96. doi: 10.1093/infdis/172.1.88.

Authors

C C Wilson¹, J T Wong, D D Girard, D P Merrill, M Dynan, D D An, S A Kalams, R P Johnson, M S Hirsch, R T D'Aquila, et al.

Affiliation

¹ Infectious Disease and Immunopathology Units, Massachusetts General Hospital, Boston 02114, USA.

PMID: 7541065
DOI: 10.1093/infdis/172.1.88

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Acquired Immunodeficiency Syndrome / drug therapy
Acquired Immunodeficiency Syndrome / immunology*
Acquired Immunodeficiency Syndrome / virology
Antiviral Agents / therapeutic use*
Base Sequence
CD4 Lymphocyte Count*
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / immunology*
Cells, Cultured
DNA Primers
DNA, Viral / blood*
Drug Therapy, Combination
HIV Infections / drug therapy
HIV Infections / immunology*
HIV Infections / virology
HIV Long Terminal Repeat
HIV Reverse Transcriptase
HIV Seropositivity / drug therapy
HIV Seropositivity / immunology*
HIV Seropositivity / virology
HIV-1* / genetics
HIV-1* / isolation & purification
Humans
Lymphocyte Activation
Molecular Sequence Data
Polymerase Chain Reaction / methods
RNA-Directed DNA Polymerase / genetics
Receptors, Antigen, T-Cell, alpha-beta / analysis

Substances

Antiviral Agents
DNA Primers
DNA, Viral
Receptors, Antigen, T-Cell, alpha-beta
HIV Reverse Transcriptase
RNA-Directed DNA Polymerase

Grants and funding

etc