Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?

Leonidas Stamatatos, Lynn Morris, Dennis R Burton & John R Mascola

Published online: 14 June 2009 | doi:10.1038/nm.1949

Abstract - | Full Text - Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? | PDF (254 KB) - Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?

GOAT links dietary lipids with the endocrine control of energy balance

Henriette Kirchner, Jesus A Gutierrez, Patricia J Solenberg, Paul T Pfluger, Traci A Czyzyk, Jill A Willency, Annette Schürmann, Hans-Georg Joost, Ronald J Jandacek, John E Hale, Mark L Heiman & Matthias H Tschöp

Published online: 05 June 2009 | doi:10.1038/nm.1997

Abstract - | Full Text - GOAT links dietary lipids with the endocrine control of energy balance | PDF (331 KB) - GOAT links dietary lipids with the endocrine control of energy balance | Supplementary information

Targeted depletion of lymphotoxin-–expressing T_H1 and T_H17 cells inhibits autoimmune disease

Eugene Y Chiang, Ganesh A Kolumam, Xin Yu, Michelle Francesco, Sinisa Ivelja, Ivan Peng, Peter Gribling, Jean Shu, Wyne P Lee, Canio J Refino, Mercedesz Balazs, Andres Paler-Martinez, Allen Nguyen, Judy Young, Kai H Barck, Richard A D Carano, Ron Ferrando, Lauri Diehl, Devavani Chatterjea & Jane L Grogan

Published online: 28 June 2009 | doi:10.1038/nm.1984

B cell–depleting antibodies have therapeutic efficacy against arthritis. Here Jane Grogan and her colleagues report a new approach to depleting pathogenic T cells. They show that lymphotoxin- is upregulated on the surface of activated T_H1 and T_H17 CD4⁺ cells, which have a pathogenic role in several autoimmune diseases, and a monoclonal antibody targeted to lymphotoxin-a can inhibit collagen-induced arthritis and EAE in mice.

Abstract - | Full Text - Targeted depletion of lymphotoxin-–expressing TH1 and TH17 cells inhibits autoimmune disease | PDF (904 KB) - Targeted depletion of lymphotoxin-–expressing TH1 and TH17 cells inhibits autoimmune disease | Supplementary information

Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease

Kim Midwood, Sandra Sacre, Anna M Piccinini, Julia Inglis, Annette Trebaul, Emma Chan, Stefan Drexler, Nidhi Sofat, Masahide Kashiwagi, Gertraud Orend, Fionula Brennan & Brian Foxwell

Published online: 28 June 2009 | doi:10.1038/nm.1987

TLR4 has a key role in driving inflammation in mouse models of arthritis and may also have a role in the human disease. The extracellular matrix protein tenascin-C is upregulated in the joints of individuals with rheumatoid arthritis. Here Kim Midwood and her colleagues show that tenascin-C is an endogenous activator of TLR4 and that it contributes to the maintenance of arthritis in mice.

Abstract - | Full Text - Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease | PDF (813 KB) - Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease | Supplementary information

HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation

Nicolas Chomont, Mohamed El-Far, Petronela Ancuta, Lydie Trautmann, Francesco A Procopio, Bader Yassine-Diab, Geneviève Boucher, Mohamed-Rachid Boulassel, Georges Ghattas, Jason M Brenchley, Timothy W Schacker, Brenna J Hill, Daniel C Douek, Jean-Pierre Routy, Elias K Haddad & Rafick-Pierre Sékaly

Published online: 21 June 2009 | doi:10.1038/nm.1972

Highly active antiretroviral therapy is unable to eliminate HIV infection because the virus persists in latently infected CD4⁺ T cells—a so-called virus reservoir. Rafick-Pierre Sekaly and his colleagues have shown that central memory CD4⁺ T cells and transitional memory CD4⁺ T cells are the main cellular reservoirs for HIV, and they suggest a mechanism that ensures the stability of this reservoir of virus.

Abstract - | Full Text - HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation | PDF (487 KB) - HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation | Supplementary information

CD4 downregulation by memory CD4⁺ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection

Coreen M Beaumier, Levelle D Harris, Simoy Goldstein, Nichole R Klatt, Sonya Whitted, John McGinty, Cristian Apetrei, Ivona Pandrea, Vanessa M Hirsch & Jason M Brenchley

Published online: 14 June 2009 | doi:10.1038/nm.1970

Natural hosts of simian immunodeficiency virus (SIV)—such as African green monkeys—have evolved to tolerate SIV infection without developing immune deficiency. Jason Brenchley and his colleagues provide a mechanism. They show that CD4⁺ T cells from these animals downregulate the CD4 receptor upon entering the memory pool. Immune functions normally attributed to CD4⁺ T cells are preserved, but the cells become resistant to SIV infection.

Abstract - | Full Text - CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection | PDF (659 KB) - CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection | Supplementary information

A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis

Tony Muchamuel, Michael Basler, Monette A Aujay, Erika Suzuki, Khalid W Kalim, Christoph Lauer, Catherine Sylvain, Eileen R Ring, Jamie Shields, Jing Jiang, Peter Shwonek, Francesco Parlati, Susan D Demo, Mark K Bennett, Christopher J Kirk & Marcus Groettrup

Published online: 14 June 2009 | doi:10.1038/nm.1978

Christopher Kirk and his colleagues have developed the first specific inhibitor of the immunoproteasome. They find that the immunoproteasome has a major role in regulating cytokine production, as well as antigen presentation, and their inhibitor has good efficacy in animal models of arthritis.

Abstract - | Full Text - A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis | PDF (509 KB) - A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis | Supplementary information

Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys

Philip R Johnson, Bruce C Schnepp, Jianchao Zhang, Mary J Connell, Sean M Greene, Eloisa Yuste, Ronald C Desrosiers & K Reed Clark

Published online: 17 May 2009 | doi:10.1038/nm.1967

Antibodies capable of neutralizing a wide array of HIV isolates are rarely elicited by the adaptive immune response during HIV infection, and it is not known how to elicit such protective antibodies by vaccination. Philip Johnson and his colleagues have circumvented this hurdle through gene transfer technology. They show that it is possible to protect monkeys from SIV infection by administering intramuscular injections of adeno-associated virus vectors that express broadly neutralizing antibodies that can access the circulation.

Abstract - | Full Text - Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys | PDF (416 KB) - Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys | Supplementary information

Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system

Ulf Schulze-Topphoff, Alexandre Prat, Timour Prozorovski, Volker Siffrin, Magdalena Paterka, Josephine Herz, Ivo Bendix, Igal Ifergan, Ines Schadock, Marcelo A Mori, Jack Van Horssen, Friederike Schröter, Alina Smorodchenko, May Htwe Han, Michael Bader, Lawrence Steinman, Orhan Aktas & Frauke Zipp

Published online: 28 June 2009 | doi:10.1038/nm.1980

Modulating the entry of inflammatory T cells into the brain could be one way to treat the autoimmune disease multiple sclerosis. Now, Frauke Zipp and colleagues demonstrate that activation of kinin receptor B1 can block autoimmune T cell migration into the brain and can therefore inhibit experimental autoimmune encephalomyelitis in mice.

First Paragraph - | Full Text - Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system | PDF (570 KB) - Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system | Supplementary information

Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71

Yorihiro Nishimura, Masayuki Shimojima, Yoshio Tano, Tatsuo Miyamura, Takaji Wakita & Hiroyuki Shimizu

Published online: 21 June 2009 | doi:10.1038/nm.1961

Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild infectious disease that can, however, occasionally lead to severe neurological impairments. These two studies, by Nishimura et al. and Yamayoshi et al., independently identify two different receptors for EV71—P-selectin glycoprotein ligand-1 ((PSGL-1) and scavenger receptor class B, member 2 (SCARB2).

First Paragraph - | Full Text - Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71 | PDF (478 KB) - Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71 | Supplementary information

Scavenger receptor B2 is a cellular receptor for enterovirus 71

Seiya Yamayoshi, Yasuko Yamashita, Jifen Li, Nobutaka Hanagata, Takashi Minowa, Taro Takemura & Satoshi Koike

Published online: 21 June 2009 | doi:10.1038/nm.1992

Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild infectious disease that can, however, occasionally lead to severe neurological impairments. These two studies, by Nishimura et al. and Yamayoshi et al., independently identify two different receptors for EV71—P-selectin glycoprotein ligand-1 ((PSGL-1) and scavenger receptor class B, member 2 (SCARB2).

First Paragraph - | Full Text - Scavenger receptor B2 is a cellular receptor for enterovirus 71 | PDF (376 KB) - Scavenger receptor B2 is a cellular receptor for enterovirus 71 | Supplementary information

Wnt signaling arrests effector T cell differentiation and generates CD8⁺ memory stem cells

Luca Gattinoni, Xiao-Song Zhong, Douglas C Palmer, Yun Ji, Christian S Hinrichs, Zhiya Yu, Claudia Wrzesinski, Andrea Boni, Lydie Cassard, Lindsay M Garvin, Chrystal M Paulos, Pawel Muranski & Nicholas P Restifo

Published online: 14 June 2009 | doi:10.1038/nm.1982

The Wnt pathway has a central role in stem cell regulation. Gattinoni et al. now show that activation of the Wnt signaling cascade in naive CD8⁺ T cells blocks their differentiation into effector T cells and triggers instead a memory stem cell–like phenotype. These T memory stem cells show enhanced antitumor efficacy in mice compared with other T cell subsets, arguing for their further evaluation in adoptive immunotherapies.

First Paragraph - | Full Text - Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells | PDF (610 KB) - Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells | Supplementary information

Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques

Ann J Hessell, Pascal Poignard, Meredith Hunter, Lars Hangartner, David M Tehrani, Wim K Bleeker, Paul W H I Parren, Preston A Marx & Dennis R Burton

Published online: 07 June 2009 | doi:10.1038/nm.1974

Studies in macaques have shown that neutralizing antibodies can offer robust protection from infection with a simian counterpart of HIV, yet these studies have also suggested that high concentrations of antibodies are required for efficient protection. Unfortunately, it's not generally thought to be feasible to elicit such high neutralizing antibody titers by vaccination. Dennis Burton and his colleagues now show that lower concentrations of antibodies can offer protection to macaques if a repeated low-dose challenge model is used—a model that may better recapitulate the acquisition of infection in humans.

First Paragraph - | Full Text - Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques | PDF (247 KB) - Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques | Supplementary information

Hematopoietic colony–stimulating factors mediate tumor-nerve interactions and bone cancer pain

Matthias Schweizerhof, Sebastian Stösser, Martina Kurejova, Christian Njoo, Vijayan Gangadharan, Nitin Agarwal, Martin Schmelz, Kiran Kumar Bali, Christoph W Michalski, Stefan Brugger, Anthony Dickenson, Donald A Simone & Rohini Kuner

Published online: 07 June 2009 | doi:10.1038/nm.1976

Pain is one of the many debilitating side effects of cancer. Now, Rohini Kuner and her colleagues show that blocking hematopoietic colony-stimulating factor signaling on neurons can inhibit pain caused by bone cancer.

First Paragraph - | Full Text - Hematopoietic colony–stimulating factors mediate tumor-nerve interactions and bone cancer pain | PDF (664 KB) - Hematopoietic colony–stimulating factors mediate tumor-nerve interactions and bone cancer pain | Supplementary information

Validated germline-competent embryonic stem cell lines from nonobese diabetic mice

Jennifer Nichols, Kenneth Jones, Jenny M Phillips, Stephen A Newland, Mila Roode, William Mansfield, Austin Smith & Anne Cooke

Published online: 02 June 2009 | doi:10.1038/nm.1996

Abstract - | Full Text - Validated germline-competent embryonic stem cell lines from nonobese diabetic mice | PDF (760 KB) - Validated germline-competent embryonic stem cell lines from nonobese diabetic mice | Supplementary information