This study, for the first time, reveals the role of M. leprae-specific CD4+TCRγδ+FoxP3+ cells in the progression and pathogenesis of leprosy. Co-culture with CD4+CD25− cells suggested the immunosuppressive nature of CD4+TCRγδ+ cells in dose-dependent manner. Isolation of CD4+TCRγδ+ cells from leprosy patients and then culture in presence of M. leprae cell wall antigens (MLCwA) along with TGF β, IPP and IL-2 suggested that these cells are M. leprae specific. TGF-β-mediated SMAD3 signalling was turned out to be major factor towards the expression of FoxP3 in these cells. SMAD3 silencing during induction of these cells barely showed the induction of FoxP3. High density of SMAD3 binding at TGFβRII in CD4+TCRγδ+FoxP3+ furthermore suggested the TGF-β-directed SMAD3 signalling in these cells. Taken together the above data, we can conclude that CD4+TCRγδ+FoxP3+ cells possess the potential to track the severity of the disease in leprosy patients.
Bibliographical noteFunding Information:
All the authors are grateful to ICMR, New Delhi for financial support. The authors are thankful to Dr. Pankaj Pathak, Department of Pathology, AIIMS, New Delhi, India, for providing assistance to perform immunoprecipitation and immunoblotting.
- CD4TCRγδFoxP3 cells