Dichotomy of cytokine profiles in patients and high-risk healthy subjects exposed to tuberculosis.
To better understand the role of cytokines in susceptible and resistant subjects exposed to Mycobacterium tuberculosis infection, intracellular gamma interferon (IFN-gamma) and interleukin-4 (IL-4) in ex vivo peripheral blood-derived CD4(+) T cells were examined by flow cytometry. Of the 37 individuals examined, 20 had clinical evidence of pulmonary tuberculosis and showed acid-fast bacilli in the sputum. Other individuals in close contact with these patients showed no evidence of disease. Patients had a higher number of CD4(+) T cells expressing IFN-gamma and IL-4 in unstimulated cultures compared to healthy subjects. Despite this, the ratio of IFN-gamma(+) to IL-4(+) CD4(+) T cells was similar in both groups. The Th1 response seen in CD4(+) T cells in patients was also observed in the overall pattern of IFN-gamma and IL-4 detected in control culture supernatants by enzyme-linked immunosorbent assay (ELISA). However, after in vitro stimulation of PBMC with heat-killed M. tuberculosis there was a significant reduction in the percentage of IFN-gamma(+) CD4(+) T cells (P < 0.001) in patients. This trend was reflected in the IFN-gamma ELISA assay with supernatants derived from stimulated cultures. However, the accumulated levels of IFN-gamma were higher than those for IL-4. The reduction of IFN-gamma(+) CD4(+) T cells resulted in the dominance of IL-4(+) CD4(+) T cells in 13 patients (P < 0.05). The elevated levels of IL-4(+) CD4(+) T cells seen in patients may contribute to the downregulation of IFN-gamma expression and the crucial effector function of CD4 T cells, leading to the persistence of disease and the immunopathology characteristically seen in patients. Preliminary data on the indicators of apoptosis in antigen-stimulated cultures in PBMC derived from patients are presented. Of the 17 high-risk healthy individuals examined, 11 differed in that, after mycobacterial-antigen stimulation, there was an enhancement in IFN-gamma(+) CD4(+) T cells.
Bhattacharyya
S
S
Department of Biotechnology, Department of Medicine, All India Institute of Medical Sciences, New Delhi 110 030, India.
Singla
R
R
Dey
A B
AB
Prasad
H K
HK
D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood*; D008875:Middle Aged; D012306:Risk; D014376:Tuberculosis / Q000276:immunology*
D015847:Interleukin-4; D007371:Interferon-gamma