HIV-Associated Cryptococcal Immune Reconstitution Inflammatory Syndrome Is Associated with Aberrant T Cell Function and Increased Cytokine Responses

David B. Meya, Samuel Okurut, Godfrey Zziwa, Stephen Cose, David R. Boulware, Edward N. Janoff

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15–20% of HIV-related mortality. A complication of initiating antiretroviral therapy (ART) following opportunistic infection is immune reconstitution inflammatory syndrome (IRIS). IRIS afflicts 10–30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4+ and CD8+ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ, and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8+ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2+/IL-17+ CD4+ T cells in patients with CM-IRIS. Moreover, CD8+ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.

Original languageEnglish (US)
Article number42
JournalJournal of Fungi
Volume5
Issue number2
DOIs
StatePublished - Jun 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Adaptive immune response
  • CD4 T cells
  • CD8 T cells
  • Cryptococcal meningitis
  • Cryptococcus
  • HIV
  • IRIS

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