Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection.

PubWeight™: 13.15‹?› | Rank: Top 0.1% | All-Time Top 10000

🔗 View Article (PMID 15793563)

Published in Nature on April 28, 2005

Authors

Joseph J Mattapallil1, Daniel C Douek, Brenna Hill, Yoshiaki Nishimura, Malcolm Martin, Mario Roederer

Author Affiliations

1: ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.

Articles citing this

(truncated to the top 100)

Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med (2008) 7.46

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med (2009) 7.01

Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol (2010) 6.55

Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature (2008) 6.17

Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science (2006) 6.06

The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol (2009) 5.99

Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice. PLoS Med (2008) 5.81

Targeting early infection to prevent HIV-1 mucosal transmission. Nature (2010) 5.05

Glycerol monolaurate prevents mucosal SIV transmission. Nature (2009) 5.02

Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J Virol (2009) 4.98

Acute HIV-1 Infection. N Engl J Med (2011) 4.84

Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med (2008) 4.68

Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239. J Virol (2006) 4.68

Challenges in the development of an HIV-1 vaccine. Nature (2008) 4.32

Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog (2013) 4.05

Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med (2009) 3.94

Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol (2007) 3.71

Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection. PLoS One (2012) 3.69

Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection. J Exp Med (2007) 3.45

Inefficient human immunodeficiency virus replication in mobile lymphocytes. J Virol (2006) 3.26

Setting the stage: host invasion by HIV. Nat Rev Immunol (2008) 3.25

Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol (2007) 3.24

HIV infection and the gastrointestinal immune system. Mucosal Immunol (2008) 3.14

Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection. PLoS Med (2006) 3.09

Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol (2012) 2.84

Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science (2009) 2.64

Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge. J Exp Med (2006) 2.60

Generation of transmitted/founder HIV-1 infectious molecular clones and characterization of their replication capacity in CD4 T lymphocytes and monocyte-derived macrophages. J Virol (2011) 2.55

CD4 T follicular helper cell dynamics during SIV infection. J Clin Invest (2012) 2.55

Expansion of HIV-specific T follicular helper cells in chronic HIV infection. J Clin Invest (2012) 2.55

Human immunodeficiency virus type 1-specific CD8+ T-cell responses during primary infection are major determinants of the viral set point and loss of CD4+ T cells. J Virol (2009) 2.51

CpG methylation controls reactivation of HIV from latency. PLoS Pathog (2009) 2.51

Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat Rev Microbiol (2009) 2.47

Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med (2012) 2.46

Understanding the benign nature of SIV infection in natural hosts. J Clin Invest (2007) 2.43

IL-15 induces CD4 effector memory T cell production and tissue emigration in nonhuman primates. J Clin Invest (2006) 2.41

Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts. Blood (2006) 2.40

The known unknowns of HPV natural history. J Clin Invest (2011) 2.39

Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection. J Virol (2007) 2.39

Trafficking of antigen-specific CD8+ T lymphocytes to mucosal surfaces following intramuscular vaccination. J Immunol (2008) 2.35

The genotype of early-transmitting HIV gp120s promotes α (4) β(7)-reactivity, revealing α (4) β(7) +/CD4+ T cells as key targets in mucosal transmission. PLoS Pathog (2011) 2.32

Recognition of a defined region within p24 gag by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I alleles. J Virol (2007) 2.32

Microbial translocation across the GI tract. Annu Rev Immunol (2012) 2.30

Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates. Proc Natl Acad Sci U S A (2007) 2.30

Going wild: lessons from naturally occurring T-lymphotropic lentiviruses. Clin Microbiol Rev (2006) 2.28

tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes. PLoS Biol (2006) 2.28

Early depletion of Mycobacterium tuberculosis-specific T helper 1 cell responses after HIV-1 infection. J Infect Dis (2008) 2.26

Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunol (2008) 2.23

HIV-1 immunopathogenesis: how good interferon turns bad. Clin Immunol (2006) 2.23

Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood (2007) 2.21

New paradigms for HIV/AIDS vaccine development. Annu Rev Med (2011) 2.21

Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy. Science (2016) 2.21

Mechanisms of gastrointestinal CD4+ T-cell depletion during acute and early human immunodeficiency virus type 1 infection. J Virol (2006) 2.19

Rapid onset of intestinal epithelial barrier dysfunction in primary human immunodeficiency virus infection is driven by an imbalance between immune response and mucosal repair and regeneration. J Virol (2007) 2.11

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. Gastroenterology (2009) 2.10

Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton. Proc Natl Acad Sci U S A (2010) 2.07

Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection. J Exp Med (2010) 2.07

Antiviral therapy during primary simian immunodeficiency virus infection fails to prevent acute loss of CD4+ T cells in gut mucosa but enhances their rapid restoration through central memory T cells. J Virol (2008) 2.06

Why primate models matter. Am J Primatol (2014) 2.05

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa. Proc Natl Acad Sci U S A (2009) 2.03

HIV-1/mycobacterium tuberculosis coinfection immunology: how does HIV-1 exacerbate tuberculosis? Infect Immun (2011) 2.03

Residual immune dysregulation syndrome in treated HIV infection. Adv Immunol (2013) 2.01

Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection. J Virol (2005) 2.01

Alpha4(+)beta7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection. Mucosal Immunol (2009) 1.96

Sex steroid hormones, hormonal contraception, and the immunobiology of human immunodeficiency virus-1 infection. Endocr Rev (2009) 1.95

Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques. Blood (2011) 1.91

HIV-1 Nef: at the crossroads. Retrovirology (2008) 1.88

Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection. J Immunol (2009) 1.87

Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts. Trends Immunol (2008) 1.86

HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature (2013) 1.84

Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive to human immunodeficiency virus type 1 infection. J Virol (2009) 1.84

Elevations in IL-10, TNF-alpha, and IFN-gamma from the earliest point of HIV Type 1 infection. AIDS Res Hum Retroviruses (2006) 1.83

Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev (2013) 1.82

CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection. Nat Med (2009) 1.81

Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infection. Mucosal Immunol (2010) 1.78

The antiviral efficacy of simian immunodeficiency virus-specific CD8+ T cells is unrelated to epitope specificity and is abrogated by viral escape. J Virol (2006) 1.78

Coinfection with HIV-1 and HCV--a one-two punch. Gastroenterology (2009) 1.78

Patterns of CD8+ immunodominance may influence the ability of Mamu-B*08-positive macaques to naturally control simian immunodeficiency virus SIVmac239 replication. J Virol (2007) 1.78

Endogenous factors enhance HIV infection of tissue naive CD4 T cells by stimulating high molecular mass APOBEC3G complex formation. J Exp Med (2006) 1.77

Intestinal macrophages and response to microbial encroachment. Mucosal Immunol (2010) 1.76

Resting naive CD4+ T cells are massively infected and eliminated by X4-tropic simian-human immunodeficiency viruses in macaques. Proc Natl Acad Sci U S A (2005) 1.75

Preserved central memory and activated effector memory CD4+ T-cell subsets in human immunodeficiency virus controllers: an ANRS EP36 study. J Virol (2007) 1.74

Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design. J Virol (2008) 1.69

Immune activation driven by CTLA-4 blockade augments viral replication at mucosal sites in simian immunodeficiency virus infection. J Immunol (2008) 1.69

Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood (2012) 1.69

Immune activation and HIV persistence: implications for curative approaches to HIV infection. Immunol Rev (2013) 1.68

Multifunctional human immunodeficiency virus (HIV) gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection. J Virol (2007) 1.67

Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection. PLoS Pathog (2009) 1.66

HIV-1 vaccine development after STEP. Annu Rev Med (2010) 1.64

The role of Th17 cytokines in primary mucosal immunity. Cytokine Growth Factor Rev (2010) 1.64

Macrophage infection via selective capture of HIV-1-infected CD4+ T cells. Cell Host Microbe (2014) 1.64

The macrophage in HIV-1 infection: from activation to deactivation? Retrovirology (2010) 1.64

HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing. Blood (2009) 1.63

Depletion of CD4⁺ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques. J Clin Invest (2011) 1.62

Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections. Blood (2012) 1.62

Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels. Mucosal Immunol (2009) 1.61

The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest. Proc Natl Acad Sci U S A (2006) 1.58

CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol Rev (2013) 1.58

Differential CD4+ T-lymphocyte apoptosis and bystander T-cell activation in rhesus macaques and sooty mangabeys during acute simian immunodeficiency virus infection. J Virol (2008) 1.56

Dynamics of immune escape during HIV/SIV infection. PLoS Comput Biol (2008) 1.54

Articles by these authors

Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med (2006) 24.38

HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood (2006) 17.38

Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science (2010) 14.91

CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med (2004) 13.55

Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J Immunol Methods (2003) 11.81

Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med (2007) 11.80

T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol (2008) 11.65

HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med (2009) 8.45

PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med (2006) 8.18

Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature (2008) 8.17

Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science (2011) 7.92

A human memory T cell subset with stem cell-like properties. Nat Med (2011) 7.47

Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis (2011) 7.41

Seventeen-colour flow cytometry: unravelling the immune system. Nat Rev Immunol (2004) 7.37

Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood (2002) 6.73

Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature (2003) 6.35

Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis (2009) 6.17

Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector. J Infect Dis (2006) 5.53

Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses. J Exp Med (2007) 5.22

HIV disease: fallout from a mucosal catastrophe? Nat Immunol (2006) 5.08

An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med (2009) 4.97

Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med (2012) 4.74

Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A (2008) 4.71

Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science (2013) 4.60

Standardization of cytokine flow cytometry assays. BMC Immunol (2005) 4.55

Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry. Nat Med (2006) 4.41

Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood (2008) 4.34

Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med (2010) 4.07

T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J Virol (2004) 4.02

Distinct lineages of T(H)1 cells have differential capacities for memory cell generation in vivo. Nat Immunol (2002) 4.00

Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med (2009) 3.94

HIV vaccine research: the way forward. Science (2008) 3.86

Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat Med (2010) 3.81

Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol (2007) 3.71

T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. Immunity (2004) 3.69

Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J Exp Med (2005) 3.63

Ex vivo identification, isolation and analysis of tumor-cytolytic T cells. Nat Med (2003) 3.60

PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors. J Clin Invest (2014) 3.54

A new "Logicle" display method avoids deceptive effects of logarithmic scaling for low signals and compensated data. Cytometry A (2006) 3.49

Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection. J Exp Med (2007) 3.45

Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis (2006) 3.40

Quality assurance for polychromatic flow cytometry. Nat Protoc (2006) 3.34

The molecular basis for public T-cell responses? Nat Rev Immunol (2008) 3.32

Amine reactive dyes: an effective tool to discriminate live and dead cells in polychromatic flow cytometry. J Immunol Methods (2006) 3.32

Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog (2010) 3.28

Vaccination in humans generates broad T cell cytokine responses. J Immunol (2004) 3.27

Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med (2006) 3.26

Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol (2007) 3.24

CD8+ T cell efficacy in vaccination and disease. Nat Med (2008) 3.20

Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis-specific CD4+ memory T lymphocyte populations. Eur J Immunol (2007) 3.18

A deep profiler's guide to cytometry. Trends Immunol (2012) 3.14

Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature (2013) 3.14

A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis (2007) 3.02

Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med (2005) 3.01

Intracellular cytokine optimization and standard operating procedure. Nat Protoc (2006) 2.96

Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A (2014) 2.95

SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. Blood (2007) 2.95

Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood (2009) 2.92

Collagen deposition limits immune reconstitution in the gut. J Infect Dis (2008) 2.85

Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol (2012) 2.84

A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles. Nat Med (2005) 2.83

Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature (2011) 2.82

The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. Clin Chem (2002) 2.71

Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J Exp Med (2006) 2.70

Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. Am J Transplant (2005) 2.70

Phase I clinical evaluation of a six-plasmid multiclade HIV-1 DNA candidate vaccine. Vaccine (2007) 2.68

Role of antigen receptor affinity in T cell-independent antibody responses in vivo. Nat Immunol (2002) 2.64

Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs. PLoS Med (2006) 2.64

Role of BCR affinity in T cell dependent antibody responses in vivo. Nat Immunol (2002) 2.63

HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc Natl Acad Sci U S A (2005) 2.61

Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge. J Exp Med (2006) 2.60

Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur J Immunol (2008) 2.59

CD4 T follicular helper cell dynamics during SIV infection. J Clin Invest (2012) 2.55

Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization. Science (2013) 2.48

The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression. J Leukoc Biol (2008) 2.44

Human immunodeficiency virus type 1 neutralization measured by flow cytometric quantitation of single-round infection of primary human T cells. J Virol (2002) 2.44

Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts. Nat Med (2009) 2.41

A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol (2006) 2.39

Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology (2011) 2.39

Systemic effects of inflammation on health during chronic HIV infection. Immunity (2013) 2.34

Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses. J Immunol (2003) 2.34

Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology (2012) 2.33

Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity. Blood (2009) 2.33

IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates. Blood (2002) 2.31

Microbial translocation across the GI tract. Annu Rev Immunol (2012) 2.30

Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med (2005) 2.30

Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Ann Neurol (2003) 2.28