Immune Response in Tuberculosis - CD4/CD68 Epitope Mapping

  • Kavitha A Sree Balaji Medical College and hospital, Chromepet, Chennai, India
  • Priavadhana Rajan Prasaad ESIC Medical College and PGIMSR, KK Nagar, Chennai, India
  • Bheema Rao G Sree Balaji Medical College and hospital, Chromepet, Chennai, India
  • Hemalatha Ganapathy Sree Balaji Medical College and hospital, Chromepet, Chennai, India
Keywords: Tuberculous Lymphadenitis, Immunity, Granuloma, Immunohistochemistry


BACKGROUND: Tuberculosis, one of the oldest recorded human afflictions, is one of the biggest killers among the infectious diseases despite the use of vaccination and antibiotics. From 21st century, tuberculosis (TB) had caused illness and death of more than eight million individuals. Every year in India 600,000 deaths occur due to TB.  The incidence and prevalence are 1.5 and 3.5 million respectively.   This is further complicated by the emergence of multi-resistant strains of Mycobacterium tuberculosis and the HIV co-pandemic.   Aim of this study was to elaborate immunological framework of tuberculous lesions through its evolution which helps to understand regional host response and counter-measures to Mycobacterium tuberculosis.   MATERIALS AND METHODS: This was a retrospective study on fifteen cases which were diagnosed as tuberculous lymphadenitis (four early lesions, six evolving lesions and five late lesions) received over one year in a tertiary medical college hospital in south India.  Histopathological features of tuberculous granuloma and its immunological evolution were studied.   RESULTS:  Early lesions were negative for CD4, with focal positivity for CD68 and diffuse strong positivity for CD45.  Evolving lesions showed focal positivity with CD4, strong positivity for CD68 and diffuse peripheral positivity with CD45.  In well-formed granulomas of the late lesions, networking of CD4 cells was seen along with CD68 positivity inside the granuloma and very few CD45 positive cells.   CONCLUSION: The accumulation of MTb-specific T cells at the site of infection may prove as useful diagnostic marker for an accurate and rapid diagnosis of active TB.  Correlation of immunology and pathology will contribute significantly to the design of novel intervention strategies. Thus, this study emphasizes on complex, dynamic and delicate interactions between mycobacteria and cells of their hosts.  


1. Laniado-Laborin R. Recent Advances in the Diagnosis and Treatment of Drug-Resistant Tuberculosis. Current Respiratory Medicine Reviews. 2017;13.
2. Ling D, Flores L, Riley L, Pai M. Commercial Nucleic-Acid Amplification Tests for Diagnosis of Pulmonary Tuberculosis in Respiratory Specimens: Meta-Analysis and Meta-Regression. PLoS ONE. 2008;3(2):e1536.
3. Winslow G, Cooper A, Reiley W, Chatterjee M, Woodland D. Early T-cell responses in tuberculosis immunity. Immunological Reviews. 2008;225(1):284-299.
4. Dorhoi A, Reece S, Kaufmann S. For better or for worse: the immune response against Mycobacterium tuberculosis balances pathology and protection. Immunological Reviews. 2011;240(1):235-251.
5. Bissell M. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Yearbook of Pathology and Laboratory Medicine. 2012;2012:298-299.
6. Russell D. Who puts the tubercle in tuberculosis?. Nature Reviews Microbiology. 2006;5(1):39-47.
7. Ulrichs T, Kaufmann S. New insights into the function of granulomas in human tuberculosis. The Journal of Pathology. 2005;208(2):261-269.
8. Ulrichs T, Kosmiadi G, Jörg S, Pradl L, Titukhina M, Mishenko V et al. Differential Organization of the Local Immune Response in Patients with Active Cavitary Tuberculosis or with Nonprogressive Tuberculoma. The Journal of Infectious Diseases. 2005;192(1):89-97.
9. Kaplan G, Post F, Moreira A, Wainwright H, Kreiswirth B, Tanverdi M et al. Mycobacterium tuberculosis Growth at the Cavity Surface: a Microenvironment with Failed Immunity. Infection and Immunity. 2003;71(12):7099-7108.
10. Azikin W. Matrix Metalloproteinase-9 (MMP-9) Level in Tuberculosis Exposed and Infected Children. American Journal of Health Research. 2017;5(1):7.
11. Barry S, Breen R, Lipman M, Johnson M, Janossy G. Impaired antigen-specific CD4+ T lymphocyte responses in cavitary tuberculosis. Tuberculosis. 2009;89(1):48-53.
12. Lin P, Rodgers M, Smith L, Bigbee M, Myers A, Bigbee C et al. Quantitative Comparison of Active and Latent Tuberculosis in the Cynomolgus Macaque Model. Infection and Immunity. 2009;77(10):4631-4642.
13. Fenhalls G, Stevens L, Bezuidenhout J, Amphlett G, Duncan K, Bardin P et al. Distribution of IFN-, IL-4 and TNF- protein and CD8 T cells producing IL-12p40 mRNA in human lung tuberculous granulomas. Immunology. 2002;105(3):325-335.
14. Barry C, Boshoff H, Dartois V, Dick T, Ehrt S, Flynn J et al. The spectrum of latent tuberculosis: Rethinking the biology and intervention strategies. Nature Reviews Microbiology. 2009.
15. Hadrup S, Bakker A, Shu C, Andersen R, van Veluw J, Hombrink P et al. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nature Methods. 2009;6(7):520-526.
16. Nemeth J, Winkler H, Zwick R, Rumetshofer R, Schenk P, Burghuber O et al. Recruitment of Mycobacterium tuberculosis specific CD4+T cells to the site of infection for diagnosis of active tuberculosis. Journal of Internal Medicine. 2009;265(1):163-168.
Original Article