TB-IRIS after initiation of antiretroviral therapy is associated with expansion of preexistent th1 responses against mycobacterium tuberculosis antigens

Ramachandran Vignesh, Nagalingeswaran Kumarasamy, Andrew Lim, Suniti Solomon, Kailapuri G. Murugavel, Pachamuthu Balakrishnan, Sunil S. Solomon, Kenneth H. Mayer, Chinnambedu R. Swathirajan, Ezhilarasi Chandrasekaran, Ambrose Pradeep, Selvamuthu Poongulali, Constance A. Benson, Martyn A. French

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The role of T-cell responses against Mycobacterium tuberculosis antigens in tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is unclear. METHODS: Peripheral blood mononuclear cells from 45 HIV patients with treated TB, of whom 12 developed TB-IRIS, were collected at weeks 0, 2, and 6 of antiretroviral therapy (ART). Production of interferon-gamma (IFN-γ) and interleukin-2 by T cells after stimulation with purified protein derivative (PPD) or early secretory antigenic target-6 (ESAT-6) and T-cell expressions of CCR5 and CXCR3 were assessed by flow cytometry. IFN-γ and CXCL10 were assayed by enzyme-linked immunosorbent assay. RESULTS: TB-IRIS patients had higher proportions of PPD- and ESAT-6-reactive IFN-γCD4 and CD3CD4 T cells at weeks 0, 2, and 6. IFN-γ levels were also higher in peripheral blood mononuclear cell culture supernatants at all times with PPD but only at weeks 2 and 6 with ESAT-6. There were few differences for interleukin-2. CXCL10 levels in supernatants after PPD and ESAT-6 stimulation were only higher at week 6. CXCR3/CCR5CD4 T cells were higher at week 2, and CCR5CD4 T cells were higher at week 6. CONCLUSIONS: TB-IRIS is associated with Th1 responses against M. tuberculosis antigens by CD4 and CD3CD4 T cells that are present before ART and amplified afterward. It is unclear if these cause immunopathology or reflect a high pathogen load.

Original languageEnglish (US)
Pages (from-to)241-248
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume64
Issue number3
DOIs
StatePublished - Nov 1 2013

Keywords

  • HIV/AIDS
  • IRIS
  • TB-IRIS
  • tuberculosis

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Vignesh, R., Kumarasamy, N., Lim, A., Solomon, S., Murugavel, K. G., Balakrishnan, P., Solomon, S. S., Mayer, K. H., Swathirajan, C. R., Chandrasekaran, E., Pradeep, A., Poongulali, S., Benson, C. A., & French, M. A. (2013). TB-IRIS after initiation of antiretroviral therapy is associated with expansion of preexistent th1 responses against mycobacterium tuberculosis antigens. Journal of Acquired Immune Deficiency Syndromes, 64(3), 241-248. https://doi.org/10.1097/QAI.0b013e31829f6df2