Suppression of HIV-1 replication by HIV-1-irrelevant CD8+ cytotoxic T lymphocytes resulting in preservation of persistently HIV-1-infected cells in vitro.
CD8+ cells of asymptomatic HIV-1 carriers (AC) contain HIV-1-specific cytotoxic T lymphocytes (CTLs) but suppress HIV-1 replication in a class I major histocompatibility complex (MHC-I)-unrestricted manner. In order to selectively investigate the HIV-1-suppressive function of CTLs apart from HIV-1-specific cytotoxicity, HIV-1-irrelevant allo-specific CTLs were established from an HIV-1-uninfected individual and their HIV-1-suppressive activity against autologous CD4+ peripheral blood mononuclear cells (PBMC) was examined. We found that these CTLs significantly suppressed both R5 and X4-HIV-1 replication in either acutely or persistently infected autologous PBMC. Although these CTLs partially killed HIV-1-infected PBMC through Fas ligand, CTLs still suppressed late steps of HIV-1 replication in the presence of neutralizing antibodies to Fas ligand. HIV-1 replication in PBMC that had been suppressed by CTLs was reversible following depletion of CTLs from culture, analogous to the previous observation for CD8+ cell-depleted PBMC of AC. Induction of HIV-1 replication by CTL-depletion was amplified by addition of newly prepared CD4+ cells or activation with staphylococcal enterotoxin B. Our results indicate that CTLs can suppress HIV-1 replication in PBMC in an antigen-nonspecific manner and preserve infected cells in a state capable of restarting HIV-1 replication and transmission.
Department of Immunotherapeutics, Medical Research Division, Tokyo Medical and Dental University, Tokyo, Japan.
Huining
H
Liu
Takashi
T
Ohashi
Takao
T
Masuda
Xin
X
Zhou
Makoto
M
Kubo
Mari
M
Kannagi
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins