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J Infect Dis. 2013 Sep;208(6):898-906. doi: 10.1093/infdis/jit271. Epub 2013 Jun 12.

Cryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-γ responses before antiretroviral therapy but not higher T-cell responses during therapy.

Author information

1
Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.

Abstract

BACKGROUND:

Cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) may be driven by aberrant T-cell responses against cryptococci. We investigated this in human immunodeficiency virus (HIV)-infected patients with treated cryptococcal meningitis (CM) commencing combination antiretroviral therapy (cART).

METHODS:

Mitogen- and cryptococcal mannoprotein (CMP)-activated (CD25+CD134+) CD4+ T cells and -induced production of interferon-gamma (IFN-γ), IL-10, and CXCL10 were assessed in whole blood cultures in a prospective study of 106 HIV-CM coinfected patients.

RESULTS:

Patients with paradoxical C-IRIS (n = 27), compared with patients with no neurological deterioration (no ND; n = 63), had lower CMP-induced IFN-γ production in 24-hour cultures pre-cART and 4 weeks post-cART (P = .0437 and .0257, respectively) and lower CMP-activated CD4+ T-cell counts pre-cART (P = .0178). Patients surviving to 24 weeks had higher proportions of mitogen-activated CD4+ T cells and higher CMP-induced CXCL10 and IL-10 production in 24-hour cultures pre-cART than patients not surviving (P = .0053, .0436 and .0319, respectively). C-IRIS was not associated with higher CMP-specific T-cell responses before or during cART.

CONCLUSION:

Greater preservation of T-cell function and higher CMP-induced IL-10 and CXCL10 production before cART are associated with improved survival while on cART. Lower CMP-induced IFN-γ production pre-cART, but not higher CMP-specific T-cell responses after cART, were risk factors for C-IRIS.

KEYWORDS:

antigen-specific T cells; cryptococcal mannoprotein; cryptococcal meningitis; cryptococcosis-associated immune reconstitution inflammatory syndrome; interferon-gamma; whole blood assay

PMID:
23766525
PMCID:
PMC3749010
DOI:
10.1093/infdis/jit271
[Indexed for MEDLINE]
Free PMC Article

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