CD4+ TCRγδ+ FoxP3+ cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients.

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 ß, IPP and IL-2 suggested that these cells are M. leprae specific. TGF-ß-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 TGFßRII in CD4+ TCRγδ+ FoxP3+ furthermore suggested the TGF-ß-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.

Intranasal administration of peptide antigens of HIV with mucosal adjuvant CpG ODN coentrapped in microparticles enhances the mucosal and systemic immune responses.

The mucosal immune system acts as a first line of defense against infection caused by luminal pathogens. Because HIV is transmitted primarily via mucosal associated tissues, particularly with sexual transmission, understanding antiviral immunity present at these sites is important. As most of the peptide antigens show poor immunogenicity when immunized alone but after incorporating the same peptide antigens along with adjuvant CpG ODN in microparticles has shown enhanced immunogenicity in the murine model. In the present study we have investigated the immunomodulatory effects of two adjuvants, CpG 1826 and CpG 2006 (Class B, Also known as type K) to the four peptide antigens of HIV such as envelope glycoproteins gp41 Leucine Zipper, gp41 fusion domain and gp120-C2 as well as regulatory protein (Nef) in microparticles, exploring nasal route with single immunization schedule. Peptide (s) alone in the microparticles elicited low peptide specific IgG and IgA peak titres in the sera, whereas the inclusion of CpG ODN with peptides in microparticles significantly enhanced peptide specific IgG and IgA peak titres and such responses were sustained for longer durations. Similarly higher SIgA response was achieved in the mucosal washes with CpG encapsulated in microparticles. Such presence of SIgA in washes was further correlated with the presence of secretory component (SC) in the respective washes. Both adjuvants induced excellent peptide specific IgG and IgA immune responses. Thus the overall study highlighted the importance of CpG ODNs as a mucosal adjuvant for weaker peptide antigens and thus can explore for developing peptide based vaccine against HIV.