Influence of Mycobacterium tuberculosis on differential activation of helper T-cells

Authors

  • J. TALREJA,

    1. Departments of * Experimental Medicine and Biotechnology and Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • A. BHATNAGAR,

    1. Departments of * Experimental Medicine and Biotechnology and Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • S. K. JINDAL,

    1. Departments of * Experimental Medicine and Biotechnology and Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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  • N. K. GANGULY

    1. Departments of * Experimental Medicine and Biotechnology and Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Jaya Talreja, PhD, Division of Allergy, Clinical Immunology & Rheumatology, Department of Medicine, 4035 Wescoe, 3901 Rainbow Blvd, The University of Kansas Medical Center, Kansas City, KS 66160–7317, USA.
 E-mail: address: jtalreja@kumc.edu

SUMMARY

Host defence against tuberculosis infection involves T-lymphocyte mediated cellular immune responses. In this study we assessed T-cell activation by studying the early signal transduction events and production of cytokines by human CD4+ T-cells. The study constituted of five groups of subjects: (a) untreated acid fast bacilli (AFB)+ve TB patients who have not started anti-tuberculosis therapy (ATT) [New]; (b) patients who have taken ATT for two months [2T]; (c) patients who have taken ATT for six months [6T]; (d) mantoux positive healthy controls [T+ve]; (e) mantoux negative healthy controls [T−ve]. We found that mantoux positive healthy controls produced significantly higher levels of IP3, intracellular Ca2+ and presented increased PKC activity when CD4+ T-cells were stimulated with M. tuberculosis H37Rv cell lysate as compared to mantoux negative controls. Furthermore, decreased expression of CD54 (ICAM-1) and reduced [Ca2+]i were seen in TB patients as compared to T+ve healthy controls. TB patients showed significantly lower levels of IL-2 and IFNγ and higher levels of IL-4 as compared to normal healthy controls, suggesting a diminished Th1 response. Thus, the reciprocal changes in cytokines, reduced [Ca2+]i levels, and CD54 expression in patients imply phenotype shifting of Th precursors to Th2 type in TB patients.

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