Acquisition of HIV type 1 resistance by beta-chemokine-producing CD4+ T cells.
The CD4+ T cell is a major target cell type for human immunodeficiency virus type 1 (HIV-1) infection. In this study, we provide evidence that the susceptibility to HIV-1 infection is variable in individual CD4+ T cells. Five CD4+ T cell clones were isolated from an HIV-1-seronegative donor and were investigated for their susceptibility to HIV-1 infection. Four CD4+ T cell clones were resistant to infection by a macrophage-tropic (R5) HIV-1 isolate whereas one clone was fully permissive. The level of susceptibility to HIV-1 correlated inversely with beta-chemokine production, including RANTES (regulated on activation, normally T cell expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta. Resistance to HIV-1 infection was abrogated by the combined use of neutralizing antibodies against these three beta-chemokines. Interestingly, a complete inhibition of HIV-1 infection was observed in peripheral blood mononuclear cells on infection induced by adding the culture supernatant or a small number of HIV-1-resistant cell clones. Our results suggest the presence of a clonal self-defense mechanism within the CD4+ T cell population in vivo that involves the secretion of beta-chemokines.
Maeda
N
N
Department of Microbiology and Molecular Virology, Tokyo Medical and Dental University, Japan.
Koyanagi
Y
Y
Misawa
N
N
Miyano-Kurosaki
N
N
Kira
J I
JI
Yamamoto
N
N
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019742:Chemokines, CC / Q000096:biosynthesis*; D002999:Clone Cells; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D009500:Neutralization Tests
D019742:Chemokines, CC