title: Polyfunctional CD4+ T-cell induction in neutralizing antibody-triggered control of simian immunodeficiency virus infection.
abstract: Rapid depletion of memory CD4(+) T cells and delayed induction of neutralizing antibody (NAb) responses are characteristics of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. Although it was speculated that postinfection NAb induction could have only a limited suppressive effect on primary HIV replication, a recent study has shown that a single passive NAb immunization of rhesus macaques 1 week after SIV challenge can result in reduction of viral loads at the set point, indicating a possible contribution of postinfection NAb responses to virus control. However, the mechanism accounting for this NAb-triggered SIV control has remained unclear. Here, we report rapid induction of virus-specific polyfunctional T-cell responses after the passive NAb immunization postinfection. Analysis of SIV Gag-specific responses of gamma interferon, tumor necrosis factor alpha, interleukin-2, macrophage inflammatory protein 1beta, and CD107a revealed that the polyfunctionality of Gag-specific CD4(+) T cells, as defined by the multiplicity of these responses, was markedly elevated in the acute phase in NAb-immunized animals. In the chronic phase, despite the absence of detectable NAbs, virus control was maintained, accompanied by polyfunctional Gag-specific T-cell responses. These results implicate virus-specific polyfunctional CD4(+) T-cell responses in this NAb-triggered virus control, suggesting possible synergism between NAbs and T cells for control of HIV/SIV replication.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Nami
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kuwano
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Miki
authors.initials: M
authors.lastname: Kawada
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D007114:Immunization; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015683:Gene Products, gag