The PD-1-PD-L pathway also plays a key role in chronic infections as well as in the suppressive tumor microenvironment [20] by contributing directly to T-cell exhaustion and lack of immune response [21]

The PD-1-PD-L pathway also plays a key role in chronic infections as well as in the suppressive tumor microenvironment [20] by contributing directly to T-cell exhaustion and lack of immune response [21]. as opposed to BT/TT (is believed to be a critical element in the pathogenesis of leprosy and its varied clinical manifestations. However, immune response at the pathologic sites of leprosy is an extremely complex process, particularly in the light of recently evidenced heterogeneity of T cell subsets. FoxP3 positive regulatory T cells (Treg) are one of the most potent hierarchic cell types suppressing the effector T F2rl1 cell function with eventual regulation of immune response elicited by the host during intracellular infections. This study shows the recovery of the cell mediated response by CD4+ T cells by inhibiting the suppressive cytokines, IL-10 and TGF- and also by blocking of the Programmed Death-1 pathway in cells isolated from lepromatous leprosy patients. Reversal of IL-17 immune response was also achieved by modulating the cytokine milieu of cell culture and hence provides us cues to counter the unresponsiveness in leprosy patients. Introduction Leprosy is DW-1350 a disease of immunological spectrum tightly correlating with the extent of pathology and clinical manifestation [1]. It is well known that T cell defect is a distinctive feature in lepromatous leprosy (LL) in contrast to that of tuberculoid leprosy (TT) patients. In between these clinical entities lie borderline tuberculoid (BT), borderline lepromatous (BL) and borderline borderline (BB) all displaying symptoms in between the two polarized forms [2]. Selective T cell unresponsiveness to the antigens of occurs among LL patients, while responsiveness to several other antigens remains intact, a phenomenon known as split anergy [3]. BT/TT patients with strong T cell reactivity against is associated with biased production of IFN- dominant immune response, while BL/LL DW-1350 patients, so called anergic and disseminated form of the disease demonstrates T cell response skewed towards IL-4 and/or IL-10 dominant cytokine production [4]. Polarized immunity against is a critical element in the pathogenesis of leprosy and plays an important role in the varied clinical manifestations of leprosy DW-1350 [5]. Biased cytokine production has also been documented at the lesional levels of both TT as well as LL forms of leprosy [6]. However, generation of Th1/Th2-like effector cells alone cannot fully explain the polarized state of immunity. Other subsets of T cells have been identified which play important role in determining host immunity [7,8]. DW-1350 Lately, FoxP3 positive regulatory T cells (Tregs) have been characterized as one of the most potent hierarchic cell type suppressing effector T cell function with eventual regulation of immune response elicited by the host during intracellular infections such as tuberculosis [9] and leishmaniasis [10,11]. The CD4+CD25+ natural regulatory Treg cells expressing the transcription factor forkhead box P3 (FoxP3) is the best characterized suppressive T-cell subset [12]. These cells are critical for the maintenance of self-tolerance and play an important role in a wide range of clinical conditions such as autoimmune diseases, transplantation rejection reactions, cancer, as well as infectious diseases [13,14]. Mediators of Treg-cell induced suppression include the inhibitory cytokines, IL?10 and TGF- [15,16]. Over representation of Treg cells in the periphery and particularly at the pathologic sites of infection has been shown to be critical in determining local immunity, thus dictating the outcome of the disease among patients suffering from various forms of tuberculosis [9]. Recently, it was revealed that FoxP3+ inducible Tregs producing TGF- may down regulate T cell responses leading to the characteristic antigen specific.