Characterization of TB-specific T Cell Responses in Highly-exposed, but Uninfected Health Care Workers in India

This study is funded and conducted under the U.S. National Institutes of Health, Fogarty International Center. PIs are Robert Bollinger, MD, MPH; Jyothi Rengarajan, MD, Emory University.

Primary Research Question 

Do health care workers who remain TST negative, despite high-exposure to TB, demonstrate evidence of TB-specific T cell immunity?

Secondary Research Question

Does an absent, transient or sustained IGRA-response to TB among highly exposed, but uninfected health workers correlate with a specific TB-specific T cell immune response phenotype?

Background

A recent cohort study at BJGMC among health care workers has demonstrated that up to 30% of medical students convert their TST from negative to positive (>10mm), within 12 months of exposure to the clinical wards.  Despite the high risk of TB exposure, some of these medical students remain TST negative.  However, it is not clear if these HCWs have lower exposure to TB or are relatively resistant to primary TB infection.  Our prior study has identified three distinct groups of HCWs who remain TST negative despite 12 months of high-risk exposure to TB-infected patients.  Some persistently TST-negative HCWs demonstrate a transient positive IGRA response (QGIT) during the 12 month exposure period.  A second group demonstrates no positive IGRA response at any time point during the 12 month exposure period.  A third group develop and sustain a positive IGRA response during the exposure period, but still do not demonstrate a positive TST at 12 months. 

The commercially available QGIT test, utilized for our cohort study, compares the level of interferon-gamma (IFN-g) produced in cell supernatant by unstimulated PBMC with PBMC stimulated with two TB antigens (ESAT-6 and CFP-10).  Scientists at Emory University’s Emory Vaccine Center have developed methods that utilize flow cytometry to more extensively characterize and quantify TB-specific T cell responses.  Therefore, we propose to utilize stored PBMC from HCWs enrolled in our cohort study to confirm whether the presence, absence or pattern of IGRA(QGIT)-responses correlates with methods characterizing the CD4 and CD8 T cell response to TB, available in Dr. Rengarajan’s laboratory at Emory.