1. Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies
- Author
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Manuel Leal, Amarendra Pegu, Michael Y. Gerner, Ilias Vagios, Sarah Andrews, Ezequiel Ruiz-Mateos, Eli Boritz, Constantinos Petrovas, Jason Hataye, Luz A. González-Hernández, Ronald N. Germain, Daniel C. Douek, Michael R. Betts, Arik Cooper, Amaranta Rivero, John R. Mascola, Perla M. Del Rio Estrada, Giuseppe Pantaleo, Yuria Ablanedo-Terrazas, David R. Ambrozak, Gustavo Reyes-Terán, Sara Ferrando-Martinez, Fernando Docobo, Joseph P. Casazza, Richard A. Koup, Kristin L. Boswell, Susan Moir, Eirini Moysi, Robert Paris, Claire Deleage, Adrian B. McDermott, Jacob D. Estes, [Petrovas, Constantinos] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Ferrando-Martinez, Sara] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Casazza, Joseph P.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Hataye, Jason] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Ambrozak, David] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Moysi, Eirini] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Boswell, Kristin L.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Gerner, Michael Y.] NIAID, Lab Syst Biol, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Germain, Ronald N.] NIAID, Lab Syst Biol, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Pegu, Amarendra] NIAID, Virol Lab, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Cooper, Arik] NIAID, Virol Lab, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Mascola, John R.] NIAID, Virol Lab, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Deleage, Claire] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Leidos Biomed Res Inc, BG 535,POB B, Frederick, MD 21702 USA, [Estes, Jacob D.] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Leidos Biomed Res Inc, BG 535,POB B, Frederick, MD 21702 USA, [Andrews, Sarah] NIAID, Immunol Core Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [McDermott, Adrian B.] NIAID, Immunol Core Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Del Rio Estrada, Perla M.] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Ablanedo-Terrazas, Yuria] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Rivero, Amaranta] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Alicia Gonzalez-Hernandez, Luz] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Reyes-Teran, Gustavo] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Boritz, Eli] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Paris, Robert] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA, [Ruiz-Mateos, Ezequiel] Univ Seville, Lab Immunovirol, Hosp Univ Virgen Rocio, Inst Biomed Sevilla,CSIC, Seville 41013, Spain, [Leal, Manuel] Univ Seville, Lab Immunovirol, Hosp Univ Virgen Rocio, Inst Biomed Sevilla,CSIC, Seville 41013, Spain, [Docobo, Fernando] Univ Seville, Lab Immunovirol, Hosp Univ Virgen Rocio, Inst Biomed Sevilla,CSIC, Seville 41013, Spain, [Vagios, Ilias] Venizeleio Hosp, Dept Histopathol, Iraklion, Crete, Greece, [Moir, Susan] NIAID, Immunoregulat Lab, Bldg 10, Bethesda, MD 20892 USA, [Pantaleo, Giuseppe] Univ Lausanne, Univ Lausanne Hosp, Dept Med, Serv Immunol & Allergy,Serv Infect Dis, CH-1011 Lausanne, Switzerland, [Pantaleo, Giuseppe] Univ Lausanne, Univ Lausanne Hosp, Swiss Vaccine Res Inst, CH-1011 Lausanne, Switzerland, [Betts, Michael R.] Univ Penn, Dept Microbiol, Ctr AIDS Res, Perelman Sch Med, Philadelphia, PA 19104 USA, [Betts, Michael R.] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA, [Gerner, Michael Y.] Univ Washington, Dept Immunol, Seattle, WA 98109 USA, VRC, NIAID, NIH, Bill and Melinda Gates Foundation, National Cancer Institute, NIH, Redes Telematicas de Investigacion Cooperativa en Salud (RETICS, Red de SIDA), Fondo de Investigacion Sanitaria, and NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
- Subjects
0301 basic medicine ,Expansion ,Adult ,Male ,Palatine Tonsil ,Replication ,Activation ,HIV Infections ,Biology ,CD8-Positive T-Lymphocytes ,HIV Antibodies ,Article ,Granzymes ,03 medical and health sciences ,Interleukin 21 ,0302 clinical medicine ,NK-92 ,Antibodies, Bispecific ,medicine ,Cytotoxic T cell ,Responses ,Humans ,Lymphocytes ,Antigen-presenting cell ,B cell ,Lymph-nodes ,Aged ,Tissue ,Perforin ,Germinal center ,virus diseases ,General Medicine ,Middle Aged ,Natural killer T cell ,Virology ,Human-immunodeficiency-virus ,030104 developmental biology ,medicine.anatomical_structure ,Phenotype ,030220 oncology & carcinogenesis ,Immunology ,Interleukin 12 ,Effector ,Rna ,Cytokines ,Female ,Lymph Nodes - Abstract
Cytolytic CD8 T cells play a crucial role in the control and elimination of virus-infected cells and are a major focus of HIV cure efforts. However, it has been shown that HIV-specific CD8 T cells are infrequently found within germinal centers (GCs), a predominant site of active and latent HIV infection. We demonstrate that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and GCs were found in LNs from treated and untreated HIV-infected individuals. This profile was associated with persistent local immune activation but did not appear to be directly related to local viral replication. Follicular CD8 (fCD8) T cells, despite compromised cytokine polyfunctionality, showed good cytolytic potential characterized by high ex vivo expression of granzyme B and perforin. We used an anti-HIV/anti-CD3 bispecific antibody in a redirected killing assay and found that fCD8 T cells had better killing activity than did non-fCD8 T cells. Our results indicate that CD8 T cells with potent cytolytic activity are recruited to GCs during HIV infection and, if appropriately redirected to kill HIV-infected cells, could be an effective component of an HIV cure strategy.
- Published
- 2017