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Natural-Killer Cell-Derived Cytolytic Molecules in HIV-Associated Pulmonary Tuberculosis—Role of Exogenous Interleukins

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Abstract

Objective

The ability of NK cells to produce cytolytic molecules is impaired during HIV infection. The objective of the present study is to investigate whether impairment in production of innate cytokines in HIV-infected individuals is responsible for the defective NK cytolytic response.

Materials and Methods

The study included 30 subjects each of normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals, and patients with HIV and TB co-infection. Intracellular staining method was adopted to enumerate the NK cells positive for cytolytic molecules. Highest stimulation of cytolytic molecules was seen with IL-15 + IL-12 combination.

Results

Stimulation with IL-15 + IL-12 showed an increased expression of perforin in NHS and HIV groups. Granzyme A was stimulated only in HIV, even with IL-15 + IL-12. Among the cytolytic molecules, maximal stimulation with IL-15 + IL-12 was seen for Granyme A and Granzyme B. Both the HIV and HIV–TB groups showed an increased response with IL-15 + IL-12 for granulysin.

Conclusion

Supplementing IL-15 + IL-12 in vitro increased the number of NK cells that are expressing cytolytic molecules in HIV-infected individuals but in HIV–TB, the critical cytolytic molecule, perforin is not apparent perhaps due to the influence of TB on HIV.

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Acknowledgement

Mr. P.V. Ramana Rao thanks the Lady Tata Memorial Trust (LTMT), Mumbai, India for providing Senior Research Fellowship. Technical support rendered by Mr. Murugesan for flow cytometry is kindly acknowledged. We gratefully thank the patients and controls for participating in the study.

Author Disclosure Statement

No competing financial interests exist.

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Authors and Affiliations

  1. Department of Immunology, Tuberculosis Research Centre (ICMR), Mayor V. R. Ramanathan Road, Chetput, Chennai, 600 031, India

    P. V. Ramana Rao, S. Ramanavelan & Alamelu Raja

  2. Government Hospital of Thoracic Medicine, Tambaram Sanatorium, Chennai, 600 047, India

    S. Rajasekaran

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  1. P. V. Ramana Rao
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  2. S. Ramanavelan
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  3. S. Rajasekaran
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  4. Alamelu Raja
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Correspondence to Alamelu Raja.

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Rao, P.V.R., Ramanavelan, S., Rajasekaran, S. et al. Natural-Killer Cell-Derived Cytolytic Molecules in HIV-Associated Pulmonary Tuberculosis—Role of Exogenous Interleukins. J Clin Immunol 30, 393–401 (2010). https://doi.org/10.1007/s10875-010-9380-y

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  • DOI: https://doi.org/10.1007/s10875-010-9380-y

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