HIV-1-specific CTLs effectively suppress replication of HIV-1 in HIV-1-infected macrophages.
Both CD4+ T cells and macrophages are major reservoirs of HIV-1. Previous study showed that HIV-1-specific cytolytic T lymphocytes (CTLs) hardly recognize HIV-1-infected CD4+ T cells because of Nef-mediated HLA class I down-regulation, suggesting that HIV-1 escapes from HIV-1-specific CTLs and continues to replicate in HIV-1-infected donors. On the other hand, the CTL recognition of HIV-1-infected macrophages and the effect of Nef-mediated HLA class I down-regulation on this recognition still remain unclear. We show a strong HIV-1 antigen presentation by HIV-1-infected macrophages. HIV-1-specific CTLs had strong abilities to suppress HIV-1R5 virus replication in HIV-1-infected macrophages and to kill HIV-1R5-infected macrophages. Nef-mediated HLA class I down-regulation minimally influenced the recognition of HIV-1-infected macrophages by HIV-1-specific CTLs. In addition, HIV-1-infected macrophages had a stronger ability to stimulate the proliferation of HIV-1-specific CTLs than HIV-1-infected CD4+ T cells. Thus, the effect of Nef-mediated HLA class I down-regulation was less critical with respect to the recognition by HIV-1-specific CTLs of HIV-infected macrophages than that of HIV-1-infected CD4+ T cells. These findings support the idea that the strong HIV-1 antigen presentation by HIV-1-infected macrophages is one of the mechanisms mediating effective induction of HIV-1-specific CTLs in the acute and early chronic phases of HIV-1 infection.
Fujiwara
Mamoru
M
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Takiguchi
Masafumi
M
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D049109:Cell Proliferation; D015536:Down-Regulation; D005434:Flow Cytometry; D015693:Gene Products, nef / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000821:virology*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus