Long-term remission of diabetes in NOD mice is induced by nondepleting anti-CD4 and anti-CD8 antibodies.
AuthorsYi Z, Diz R, Martin AJ, Morillon YM, Kline DE, Li L, Wang B, Tisch R,
JournalDiabetes
PubMed ID22751694
Residual ß-cells found at the time of clinical onset of type 1 diabetes are sufficient to control hyperglycemia if rescued from ongoing autoimmune destruction. The challenge, however, is to develop an immunotherapy that not only selectively suppresses the diabetogenic response and efficiently reverses diabetes, but also establishes long-term ß-cell-specific tolerance ... More
Techniques to improve the direct ex vivo detection of low frequency antigen-specific CD8+ T cells with peptide-major histocompatibility complex class I tetramers.
AuthorsChattopadhyay PK, Melenhorst JJ, Ladell K, Gostick E, Scheinberg P, Barrett AJ, Wooldridge L, Roederer M, Sewell AK, Price DA,
JournalCytometry A
PubMed ID18836993
'The ability to quantify and characterize antigen-specific CD8+ T cells irrespective of functional readouts using fluorochrome-conjugated peptide-major histocompatibility complex class I (pMHCI) tetramers in conjunction with flow cytometry has transformed our understanding of cellular immune responses over the past decade. In the case of prevalent CD8+ T cell populations that ... More
The survival of memory CD8 T cells that is mediated by IL-15 correlates with sustained protection against malaria.
AuthorsZarling S, Berenzon D, Dalai S, Liepinsh D, Steers N, Krzych U
JournalJ Immunol
PubMed ID23589611
'Ag-specific memory T cell responses elicited by infections or vaccinations are inextricably linked to long-lasting protective immunity. Studies of protective immunity among residents of malaria endemic areas indicate that memory responses to Plasmodium Ags are not adequately developed or maintained, as people who survive episodes of childhood malaria are still ... More
Role of NK cells in host defense against pulmonary type A Francisella tularensis infection.
'Pneumonic tularemia is a potentially fatal disease caused by the Category A bioterrorism agent Francisella tularensis. Understanding the pulmonary immune response to this bacterium is necessary for developing effective vaccines and therapeutics. In this study, characterization of immune cell populations in the lungs of mice infected with the type A ... More
Measles virus vaccine attenuation: suboptimal infection of lymphatic tissue and tropism alteration.
'The mechanisms of measles virus (MV) vaccine attenuation are insufficiently characterized. Because the Edmonston vaccine strain can enter cells through CD46 in addition to the primary MV receptor signaling lymphocyte activation molecule (SLAM or CD150), we asked whether and how its tropism is altered. In human tonsillar tissue, this vaccine ... More
Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue.
AuthorsIijima N, Mattei LM, Iwasaki A,
JournalProc Natl Acad Sci U S A
PubMed ID21173243
'Monocytes patrol various tissues for signs of infection and inflammation. Inflammatory monocytes enter peripheral tissues at sites of microbial infection and differentiate into dendritic cells and macrophages. Here, we examined the importance of monocytes in primary mucosal infection with herpes simplex virus 2 (HSV-2), and demonstrate that monocyte-derived APCs are ... More
Decreases in IL-7 levels during antiretroviral treatment of HIV infection suggest a primary mechanism of receptor-mediated clearance.
AuthorsHodge JN, Srinivasula S, Hu Z, Read SW, Porter BO, Kim I, Mican JM, Paik C, Degrange P, Di Mascio M, Sereti I,
JournalBlood
PubMed ID21778338
'IL-7 is essential for T-cell homeostasis. Elevated serum IL-7 levels in lymphopenic states, including HIV infection, are thought to be due to increased production by homeostatic feedback, decreased receptor-mediated clearance, or both. The goal of this study was to understand how immune reconstitution through antiretroviral therapy (ART) in HIV(+) patients ... More
Safety and immunogenicity of DNA prime and modified vaccinia ankara virus-HIV subtype C vaccine boost in healthy adults.
AuthorsHayes P, Gilmour J, von Lieven A, Gill D, Clark L, Kopycinski J, Cheeseman H, Chung A, Alter G, Dally L, Zachariah D, Lombardo A, Ackland J, Sayeed E, Jackson A, Boffito M, Gazzard B, Fast PE, Cox JH, Laufer D,
JournalClin Vaccine Immunol
PubMed ID23345581
'A randomized, double-blind, placebo-controlled phase I trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of 3 doses of DNA vaccine (Advax) plus 1 dose of recombinant modified vaccinia virus Ankara (MVA) (TBC-M4) or 3 doses of TBC-M4 alone (groups A and B, respectively). Both ... More
Distinct chemokine receptor axes regulate Th9 cell trafficking to allergic and autoimmune inflammatory sites.
AuthorsKara EE, Comerford I, Bastow CR, Fenix KA, Litchfield W, Handel TM, McColl SR,
Journal
PubMed ID23797668
Migration of Th cells to peripheral sites of inflammation is essential for execution of their effector function. The recently described Th9 subset characteristically produces IL-9 and has been implicated in both allergy and autoimmunity. Despite this, the migratory properties of Th9 cells remain enigmatic. In this study, we examined chemokine ... More
Evaluation of the safety and immunogenicity in rhesus monkeys of a recombinant malaria vaccine for Plasmodium vivax with a synthetic Toll-like receptor 4 agonist formulated in an emulsion.
AuthorsLumsden JM, Pichyangkul S, Srichairatanakul U, Yongvanitchit K, Limsalakpetch A, Nurmukhambetova S, Klein J, Bertholet S, Vedvick TS, Reed SG, Sattabongkot J, Bennett JW, Polhemus ME, Ockenhouse CF, Howard RF, Yadava A,
JournalInfect Immun
PubMed ID21690242
Plasmodium vivax is the major cause of malaria outside sub-Saharan Africa and inflicts debilitating morbidity and consequent economic impacts in developing countries. In order to produce a P. vivax vaccine for global use, we have previously reported the development of a novel chimeric recombinant protein, VMP001, based on the circumsporozoite ... More
Enhancing blood-stage malaria subunit vaccine immunogenicity in rhesus macaques by combining adenovirus, poxvirus, and protein-in-adjuvant vaccines.
AuthorsDraper SJ, Biswas S, Spencer AJ, Remarque EJ, Capone S, Naddeo M, Dicks MD, Faber BW, de Cassan SC, Folgori A, Nicosia A, Gilbert SC, Hill AV,
JournalJ Immunol
PubMed ID21098232
Protein-in-adjuvant formulations and viral-vectored vaccines encoding blood-stage malaria Ags have shown efficacy in rodent malaria models and in vitro assays against Plasmodium falciparum. Abs and CD4(+) T cell responses are associated with protective efficacy against blood-stage malaria, whereas CD8(+) T cells against some classical blood-stage Ags can also have a ... More
Stimulation of the liver X receptor pathway inhibits HIV-1 replication via induction of ATP-binding cassette transporter A1.
AuthorsMorrow MP, Grant A, Mujawar Z, Dubrovsky L, Pushkarsky T, Kiselyeva Y, Jennelle L, Mukhamedova N, Remaley AT, Kashanchi F, Sviridov D, Bukrinsky M,
JournalMol Pharmacol
PubMed ID20479131
Cholesterol plays an important role in the HIV life cycle, and infectivity of cholesterol-depleted HIV virions is significantly impaired. Recently, we demonstrated that HIV-1, via its protein Nef, inhibits the activity of the major cellular cholesterol transporter ATP binding cassette transporter A1 (ABCA1), suggesting that the virus may use this ... More
Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.
AuthorsGriffiths SJ, Riddell NE, Masters J, Libri V, Henson SM, Wertheimer A, Wallace D, Sims S, Rivino L, Larbi A, Kemeny DM, Nikolich-Zugich J, Kern F, Klenerman P, Emery VC, Akbar AN
JournalJ Immunol
PubMed ID23636061
The mechanisms regulating memory CD8(+) T cell function and homeostasis during aging are unclear. CD8(+) effector memory T cells that re-express CD45RA increase considerably in older humans and both aging and persistent CMV infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated ... More
Induction of heat shock proteins in cerebral cortical cultures by celastrol.
AuthorsChow AM, Tang DW, Hanif A, Brown IR
JournalCell Stress Chaperones
PubMed ID22865541
Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) are 'protein misfolding disorders' of the mature nervous system that are characterized by the accumulation of protein aggregates and selective cell loss. Different brain regions are impacted, with Alzheimer's affecting cells in the cerebral cortex, Parkinson's targeting dopaminergic cells in the ... More
Restricted replication of xenotropic murine leukemia virus-related virus in pigtailed macaques.
AuthorsDel Prete GQ, Kearney MF, Spindler J, Wiegand A, Chertova E, Roser JD, Estes JD, Hao XP, Trubey CM, Lara A, Lee K, Chaipan C, Bess JW, Nagashima K, Keele BF, Macallister R, Smedley J, Pathak VK, Kewalramani VN, Coffin JM, Lifson JD
JournalJ Virol
PubMed ID22238316
Although xenotropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic in vivo infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential that ... More