Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation.
Because stimulation of CD4+ lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4+ T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4+ T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of CD4+ T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.
Levine
B L
BL
Naval Medical Research Institute, Bethesda, Maryland 20889, USA.
Mosca
J D
JD
Riley
J L
JL
Carroll
R G
RG
Vahey
M T
MT
Jagodzinski
L L
LL
Wagner
K F
KF
Mayers
D L
DL
Burke
D S
DS
Weislow
O S
OS
St Louis
D C
DC
June
C H
CH
D000911:Antibodies, Monoclonal / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002455:Cell Division; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D016662:Virus Integration; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D018925:Chemokines; D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins