title: Exposure of resting peripheral blood T cells to HIV-1 particles generates CD25+ killer cells in a small subset, leading to induction of apoptosis in bystander cells.
abstract: Apoptosis is a major mechanism whereby HIV-1 depletes uninfected CD4+ and CD8+ T cells. We previously showed that resting peripheral blood T cells derived from healthy donors were killed by an apoptotic mechanism after adsorption to gp120-containing, protease-defective HIV-1 (L-2) particles, more effectively than parental wild-type LAI adsorption or rgp 120-mediated CD4 cross-linking, followed by mitogenic stimulation. Here, we present evidence that the L-2 particle-based apoptosis was induced both in CD4+ and CD8+ cells by generation of effector cells which were mainly derived from a resting memory CD4+CD38- subset. This subset enhanced the CD25 expression on the surface and secreted IFN-gamma in the culture supernatant after L-2 particle exposure. Significant elevation of Fas ligand mRNA was found in the subset by L-2 particle exposure, while expression of Fas antigen on uninfected T cells was induced by exposure to IFN-gamma. These results indicate that L-2 particles can shift the CD4+CD38- subpopulation from a resting to an activated state, and this activation leads to killing of bystander CD4+ and CD8+ T cells by a Fas-mediated mechanism. In fact, purified CD4+CD38- cells exposed to L-2 particles were converted into effector cells that were able to kill autologous as well as allogenic target T cells pretreated with IFN-gamma. Further, we found that the observation of apoptosis due to L-2 particles was a more general phenomenon, that also occurred with Thai primary HIV-1 isolates. These results suggest that such specific types of HIV-1 particles may play a major role in the induction of apoptosis for both bystander CD4+ and CD8+ T cells, through inappropriate activation of CD4+CD38- cells.
authors.affiliation: Section of Serology, Hokkaido University, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kameoka
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Fujinaga
authors.forename: W
authors.initials: W
authors.lastname: Auwanit
authors.forename: R B
authors.initials: RB
authors.lastname: Luftig
authors.forename: K
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000235:genetics; D003673:Defective Viruses / Q000276:immunology; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000097:blood / Q000209:etiology / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2