Similar observations were made in case of endemic control and cured patients of VL wherein strong T cell proliferation and IFN-c production was induced by the pooled form of four histone proteins as compared to its other counterparts. Thus, individuals who control parasite burden successfully either following treatment in the case of patients or due to adequate immunity, as in endemic contacts, exhibit good T cell reactivity to the Leishmania histone proteins. The presence of a positive immune response in all the eight endemic contacts indicates towards the high frequency of subclinical infection in an endemic area such as Bihar,Astragaloside India as has been reported in other endemic parts of the world. It is well established that recovery from Leishmania infection, relies on induction of the Th1 response particularly the production of IFN-c and IL-12 and improved expression of iNOS. Some of the recombinant antigens have previously been shown to induce lymphocyte proliferation and IFN-c production in subjects cured of visceral and in patients with cutaneous or mucosal leishmaniasis. SLD has been observed to stimulate PBMCs from L. donovaniinfected individuals eliciting a mixed Thl- and Th2- type immune response, but in this study, we noticed that all the recombinant histone proteins of L. donovani particularly the pooled rLdH2-4 shifted 13-Dehydroxyindaconintine this pattern towards an exclusive Thl cytokine profile. These recombinant proteins stimulated PBMCs from cured and infected patients to secrete TNF-a and stimulated T cells from all the cured/infected patients to proliferate and produce IFN-c associated with protective immunity. Cytokines appear to be essential mediators of immunity to Leishmania wherein IFN-c and TNF-a synergize to induce leishmanicidal activity in macrophages. In our study, TNF-a and IL-12 but not IL-10 were produced by cured/patient PBMCs stimulated with rLdHistones. This may be due to the relatively lower level of either TNF-a or IL-12 produced by patient PBMCs, as well as the ability of IFN-c, produced in high amounts by patient PBMCs, to inhibit the production of IL-10. Further, it was observed that rLdHistone proteins down-regulated the levels of IL-10 in patient PBMCs.