This study would be the first of its kind in the field
of human VL, as none of the reports dealt with human iNKT cells and their dynamics with the therapy. A belief was that CD1d-reactive cells must be expressing invariant TCR (Vα24 and Vβ11 in human) (1–3). In contrast, our finding suggests that all invariant TCR-expressing cells (iNKT) may not be solely reactive to the CD1d, especially in diseased condition, as evident from their proportional frequency (15). If CD1d-reactive NKT cells are approximately 0·2–0·4% of total lymphocyte, then what could be the reactivity of remaining iNKT cells? (approximately 1% of total lymphocyte). It indicates that all iNKT cells may not be CD1d Pritelivir reactive. Definition of human iNKT cells is further compounded by the strange observation
of a novel population with Vβ11+, but CD161− (Figure 1b,d). This population may be expressing other NK cell marker of NK cell recognition complex. mTOR inhibitor But absence of a stimulatory/activating receptor CD161, which recognizes non-MHC ligand, potentiates possible function of this novel subset in a MHC-dependent manner. However, a detailed study is required in this regard. Duality in function of the enriched iNKT cells at the disease site will be crucial in dictating the disease outcome. Dichotomies in the functional behaviour of iNKT cells are in support for the existence of iNKT-1 (IFN-γ producing) and iNKT-2 (IL-4 producing), very similar to Th-1 and Th-2 (16). The antigen-specific response of these functionally divergent cells will be relevant in context of the pathology of VL. They may have some role in the early modulation/triggering of forthcoming immune response at disease site. This study was supported by Department of Biotechnology (Government cAMP of India) for funding the work (Grant No.: BT/PR6737/Med/14/871/2005).
In addition, we thank the Council of Scientific and Industrial Research (CSIR), Government of India, for providing fellowship to Dr. Ambak K. Rai. The authors thank all the patients and control subjects who voluntarily agreed to participate in this study. We also thank Dr. Pradeep Dagur and Dr. Beenu Joshi, (JALMA, Agra, India) for helping in preparation of Leishmania antigen and extremely grateful to Dr. R. Viswakarma (NII, New Delhi, India) for providing LPG. Figure S1. MNCs derived from blood of patients were stained under various staining conditions (a) Preloaded CD1d dimer with aGalcer, but no secondary fluorescent antibody, (b) unloaded CD1d dimer, with secondary fluorescent antibody and (c) preloaded CD1d dimer with aGalcer, with secondary fluorescent antibody. Figure S2. MNCs were incubated with CD1d dimer under following conditions (a) Loaded CD1d dimer, no aIgG1 FITC, (b) unloaded CD1d dimer, aIgG1 FITC, (c) Loaded CD1d dimer (in 10× molar access), aIgG1 FITC and (d) Loaded CD1d dimer (in 20× molar access), aIgG1 FITC. Figure S3.