PURPOSE: Host immune response against M. tuberculosis critically involves IFN-g; biased Th1 effector cells. These cells are determine the local immune response thus dictating the clinical manifestation. Understanding the mechanisms of their recruitment to the site of pathology is important for identifying the target event(s) of putative immune intervention for therapy. Migration of locally infiltrating effector T cells to the pathological site(s) depending on their chemokine receptor expression profiles and respective ligands, determine the local immune response thus dictating the clinical progression of human tuberculosis.
METHODS: The study included 35 patients with TB (TB pleural effusion, n=25 & miliary TB, n=10). Here, we further show the expression of three homing receptors CXCR3, CCR5 and CD11a at single cell level on T cells at the local pathological site samples (pleural fluid and bronchoalveolar lavage) as well as autologous peripheral blood using flow cytometry.
RESULTS: Significant enrichment of CXCR3, CCR5 dual positive and single positive T cells was observed at local pathological site over peripheral blood in both studied forms of TB. Interestingly, expression of these receptors was extremely high on activated lymphocytes than on normal lymphocytes in TB pleural fluid. Moreover, it was observed that all CCR5+ cells were invariably positive for CXCR3 but all CXCR3+ cells didn't co-express CCR5 in pleural fluid of TB-PE whereas the situation was reverse in bronchoalveolar lavage of miliary TB. Furthermore, M. tuberculosis antigen specific stimulation resulted in higher level of IFN- production by these cells in pleural fluid of TB pleural effusion. Additionally, RANTES and IP-10 played hierarchic role in the selective migration of CXCR3+CCR5+ T cells in TB pleural effusion as confirmed by in-vitro chemotaxis experiments using blocking antibodies.
CONCLUSION: Data suggests that CXCR3, CCR5 and their ligands (RANTES, IP-10) play hierarchic role in selective recruitment of highly polarized Th1 cells at the tubercular pathological site.
CLINICAL IMPLICATIONS: Our data can be utilized to develop therapeutic modalities in treating the patient of tuberculosis.
DISCLOSURE: Pradip Saha, No Financial Disclosure Information; No Product/Research Disclosure Information