The phenotype of the Cryptococcus-specific CD4+ memory T-cell response is associated with disease severity and outcome in HIV-associated cryptococcal meningitis.
Background: Correlates of immune protection in patients with human immunodeficiency virus (HIV)-associated cryptococcal meningitis are poorly defined. A clearer understanding of these immune responses is essential to inform rational development of immunotherapies.Methods: Cryptococcal-specific perip...
| Publicado en: | Journal of Infectious Diseases Vol. 207; no. 12; pp. 1817 - 1829 |
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| Autores principales: | , , , , , , , |
| Formato: | research randomized controlled trial Journal Article |
| Publicado: |
Oxford University Press / USA
Jun2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104287823&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104287823 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00221899 1YU jtl: Journal of Infectious Diseases issn: 00221899 maglogo: N pubinfo: dt: Jun2013 vid: 207 iid: 12 pid: 622 pub: Oxford University Press / USA artinfo: ui: 104287823 NLM23493728 2012121146 10.1093/infdis/jit099 NLM23493728 PMC3654748 104287823 ppf: 1817 ppct: 12 formats: tig: atl: The phenotype of the Cryptococcus-specific CD4+ memory T-cell response is associated with disease severity and outcome in HIV-associated cryptococcal meningitis. aug: au: Jarvis, Joseph N Casazza, Joseph P Stone, Hunter H Meintjes, Graeme Lawn, Stephen D Levitz, Stuart M Harrison, Thomas S Koup, Richard A affil: Research Centre for Infection and Immunity, Division of Clinical Sciences, St. George's University of London. sug: subj: Antigens, Fungal Immunology T Lymphocytes Immunology Cryptococcus Immunology Human Immunodeficiency Virus Immunology HIV Infections Immunology Meningitis, Cryptococcal Immunology Adult Prospective Studies Cryptococcus Classification Cytokines Cerebrospinal Fluid Female HIV Infections Complications HIV Infections Human Interferons Cerebrospinal Fluid Male Meningitis, Cryptococcal Complications Meningitis, Cryptococcal Microbiology Meningitis, Cryptococcal Mortality Phenotype Severity of Illness Indices South Africa Tumor Necrosis Factor Cerebrospinal Fluid Viral Load Randomized Controlled Trials Adult: 19-44 years Female Male ab: Background: Correlates of immune protection in patients with human immunodeficiency virus (HIV)-associated cryptococcal meningitis are poorly defined. A clearer understanding of these immune responses is essential to inform rational development of immunotherapies.Methods: Cryptococcal-specific peripheral CD4(+) T-cell responses were measured in 44 patients with HIV-associated cryptococcal meningitis at baseline and during follow-up. Responses were assessed following ex vivo cryptococcal mannoprotein stimulation, using 13-color flow-cytometry. The relationships between cryptococcal-specific CD4(+) T-cell responses, clinical parameters at presentation, and outcome were investigated.Results: Cryptococcal-specific CD4(+) T-cell responses were characterized by the production of macrophage inflammatory protein 1α, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α). Conversely, minimal interleukin 4 and interleukin 17 production was detected. Patients surviving to 2 weeks had significantly different functional CD4(+) T-cell responses as compared to those who died. Patients with a response predominantly consisting of IFN-γ or TNF-α production had a 2-week mortality of 0% (0/20), compared with 25% (6/24) in those without this response (P = .025). Such patients also had lower fungal burdens (10 400 vs 390 000 colony-forming units/mL; P < .001), higher cerebrospinal fluid lymphocyte counts (122 vs 8 cells/μL; P < .001), and a trend toward faster rates of clearance of infection.Conclusions: The phenotype of the peripheral CD4(+) T-cell response to Cryptococcus was associated with disease severity and outcome in HIV-associated cryptococcal meningitis. IFN-γ/TNF-α-predominant responses were associated with survival. pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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