Program Schedule

In vitro polyfunctional CD4 T cell correlates of diagnostic tests for latent TB in HIV-infected subjects

Session: Poster Abstract Session: HIV: Comorbidities and Coinfections
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
  • Cytokine correlates of LTBI in HIV.pdf (479.3 kB)
  • Background: Tuberculin skin test (TST) is a low cost means of determining the presence of latent tuberculosis (LTBI) in immunocompetent patients. However, few studies have examined the cytokine correlates of TB control in TST- versus TST+ subjects among HIV+ cohorts. This study examines TB-specific CD4 single cytokine and polyfunctional profiles of TST- and LTBI in HIV+ subjects.

    Methods: HIV+ adults recruited in Kampala, Uganda were differentiated into 2 groups: LTBI (>5mm response to the tuberculin skin test (TST) and negative chest x-ray; n=15), or TST- (TST <5 mm and chest x-ray; n=15). Interferon gamma release assay (IGRA) was also performed for each subject. Multicolor flow analysis was performed on PBMC stimulated with either PPD or mitogen, and frequencies of IL-2, IL-17, IFN-γ and TNF-α secreting cells were determined within the memory subset of CD4 T cells. Polyfunctionality was determined using FlowJo and SPICE software.

    Results: PPD-specific CD4+ T cell secretion of TNF-α and IFN-γ was higher in LTBI compared with TST- group (p=0.001 and p=0.002 respectively). In the IGRA+ group there was greater secretion of TNF-α compared with IGRA- though this difference was borderline (p=0.05). IL-2, IFN-γ and TNF-α all correlated with clinical response in terms size of PPD-induced induration or IGRA. Frequency of polyfunctional cells among the TST+ group was greater than and IGRA+ (p=0.04). TNF-α was the dominant cytokine in the TST+ group as 4/5 phenotypes of responding cells all generate either TNF-α alone or in combination with IFN-γ or IL-2. Both TNF-α and IL-2 were dominant among the single cytokine secretors in IGRA+ group. IFN-γ secreting cells are much more frequent in TST+ than IGRA+ subjects.

    Conclusion: CD4+ T cell cytokine responses to TB-specific antigens were significantly higher in LTBI compared to TST- HIV+ adults. While IL-2, IFN-γ and TNF-α all appear to be correlates of LTBI, TNF-α is the dominant cytokine in this regard. Perhaps measurement of TNF-α secretors to diagnostic testing for latent TB could add sensitivity but may reduce specificity. Differences exist between polyfunctional cytokine profiles of TST+ and IGRA+ HIV+ individuals which may account for difference in test performance.

    Puja Van Epps, MD1,2, Sankar Sridaran2, Htin Aung1, Michael Betts3, Zahara Toosi2 and David Canaday, MD1,2, (1)Geriatric Research Education & Clinical Center (GRECC), Louis Stokes Cleveland VA Medical Center, Cleveland, OH, (2)Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH, (3)Microbiology, University of Pennsylvania, Philadelphia, Philadelphia, PA


    P. Van Epps, None

    S. Sridaran, None

    H. Aung, None

    M. Betts, None

    Z. Toosi, None

    D. Canaday, None

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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