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Infection and Immunity, November 1999, p. 5597-5603, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Dichotomy of Cytokine Profiles in Patients and High-Risk Healthy Subjects Exposed to Tuberculosis

S. Bhattacharyya,1 R. Singla,2 A. B. Dey,1 and H. K. Prasad1,*

Department of Biotechnology and Department of Medicine, All India Institute of Medical Sciences,1 and LRS Institute of TB and Allied Diseases,2 New Delhi 110 030, India

Received 1 February 1999/Returned for modification 12 March 1999/Accepted 13 July 1999

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.

* Corresponding author. Mailing address: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110 029, India. Phone: 091-011-659-4994. Fax: 091-011-686-2663. E-mail: hkp{at}aiims.ernet.in.

Infection and Immunity, November 1999, p. 5597-5603, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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