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The Pathology of Lymphocytes, Histiocytes, and Immune Mechanisms in Mycobacterium tuberculosis Granulomas

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  • 1 Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and National Health Laboratory Service (NHLS), Johannesburg, South Africa;
  • 2 South African Technology Network, Durban, South Africa

ABSTRACT

Granuloma formation is the pathologic hallmark of tuberculosis (TB). Few studies have detailed the exact production of cytokines in human granulomatous inflammation and little is known about accessory molecule expressions in tuberculous granulomas. We aimed to identify some of the components of the immune response in granulomas in HIV-positive and -negative lymph nodes. We investigated the immunohistochemical profiles of CD4+, CD8+, CD68+, Th-17, Forkhead box P3 (FOXP3) cells, accessory molecule expression (human leukocyte antigen [HLA] classes I and II), and selected cytokines (interleukins 2, 4, and 6 and interferon-γ) of various cells, in granulomas within lymph nodes from 10 HIV-negative (−) and 10 HIV-positive (+) cases. CD4+ lymphocyte numbers were retained in HIV− granulomas, whereas CD4+:CD8 + cell were reversed in HIV+ TB granulomas. CD68 stained all histiocytes. Granulomas from the HIV+ group demonstrated a significant increase in FOXP3 cells. Interleukin-2 cytoplasmic expression was similar in both groups. Interferon-gamma (IFN-γ) expression was moderately increased, IL-6 was statistically increased and IL-4 expression was marginally lower in cells from HIV− than HIV+ TB granulomas. Greater numbers of cells expressed IFN-γ and IL-6 than IL-2 and IL-4 in HIV− TB granulomas. This study highlights the varied cytokine production in HIV-positive and -negative TB granulomas and indicates the need to identify localized tissue factors that play a role in mounting an adequate immune response required to halt infection. Although TB mono-infection causes variation in cell marker expression and cytokines in granulomas, alterations in TB and HIV coinfection are greater, pointing toward evolution of microorganism synergism.

Author Notes

Address correspondence to Reubina Wadee, University of the Witwatersrand/National Health Laboratory Service (NHLS), Rm. 3L30, University of the Witwatersrand, School of Pathology, 7 York Rd., Parktown, Johannesburg 2193, Republic of South Africa. E-mail: reubinawadee@gmail.com

Disclosure: The experimental work of this manuscript has been submitted and awarded by the University of the Witwatersrand for the degree of Master of Medicine, to R. Wadee.

Financial support: This research has been funded by the University of the Witwatersrand.

Authors’ addresses: Reubina Wadee, Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and National Health Laboratory Service (NHLS), Johannesburg, South Africa, E-mail: reubinawadee@gmail.com. Ahmed A. Wadee, South African Technology Network, Durban, South Africa, E-mail: ahmed@satn.co.za.

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