Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load.

Journal article

Distinct IFN-gamma and IL-2 profiles of Ag-specific CD4(+) T cells have recently been associated with different clinical disease states and Ag loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis Ag-specific T cells secreting IFN-gamma and IL-2 in 23 patients with untreated active tuberculosis when bacterial and Ag loads are high and after curative treatment, when Ag load is reduced. The frequencies of M. tuberculosis Ag-specific IFN-gamma-secreting T cells declined during 28 mo of follow-up with an average percentage decline of 5.8% per year (p = 0.005), while the frequencies of Ag-specific IL-2-secreting T cells increased during treatment (p = 0.02). These contrasting dynamics for the two cytokines led to a progressive convergence of the frequencies of IFN-gamma- and IL-2-secreting cells over 28 mo. Simultaneous measurement of IFN-gamma and IL-2 secretion at the single-cell level revealed a codominance of IFN-gamma-only secreting and IFN-gamma/IL-2 dual secreting CD4(+) T cells in active disease that shifted to dominance of IFN-gamma/IL-2-secreting CD4(+) T cells and newly detectable IL-2-only secreting CD4(+) T cells during and after treatment. These distinct T cell functional signatures before and after treatment suggest a novel immunological marker of mycobacterial load and clinical status in tuberculosis that now requires validation in larger prospective studies.

Authors: Millington, K; Innes, J; Hackforth, S; Hinks, T; Deeks, J

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 178
• Issue: 8
• Pages: 5217-5226
• Publication date: 2007-04-01
• DOI: 10.4049/jimmunol.178.8.5217
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Aged, 80 and over; Interleukin-2; Adult; Humans; T-Lymphocytes; Interferon-gamma; Bacterial Proteins; Follow-Up Studies; Middle Aged; Female; Male; Mycobacterium tuberculosis; Adolescent; Aged; Antigens, Bacterial