Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The phenotype of the cryptococcus-specific CD4
+
memory T-cell response is associated with disease severity and outcome in HIV-associated cryptococcal meningitis
Journal of Infectious Diseases, Volume 207, No. 12, Year 2013
Notification
URL copied to clipboard!
Description
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. © 2013 The Author. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3654748/bin/supp_207_12_1817__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3654748/bin/supp_jit099_jit099supp.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3654748/bin/supp_jit099_jit099supp_fig1.jpg
Authors & Co-Authors
Jarvis, Joseph N.
Unknown Affiliation
Casazza, Joseph P.
Unknown Affiliation
Stone, Hunter H.
Unknown Affiliation
Meintjes, Graeme Ayton
Unknown Affiliation
Lawn, Stephen D.
Unknown Affiliation
Levitz, Stuart M.
Unknown Affiliation
Harrison, Thomas Stephen
Unknown Affiliation
Koup, Richard A.
Unknown Affiliation
Statistics
Citations: 118
Authors: 8
Affiliations: 9
Identifiers
Doi:
10.1093/infdis/jit099
ISSN:
00221899
Research Areas
Cancer
Infectious Diseases
Study Design
Cohort Study