In the view of limited drug options and possible emergence of drug resistance,it is widely recognized that vaccination is essential in control and eventual elimination of global leishmanial infection.Till date killed Leishmania parasites,various native and recombinant vaccine agents,such as gp63,gp46,m2,PSA2,TSA,LACK,LmsT1,Leish111f etc.,have been evaluated but none achieved the required immunity to control pathogenesis.Leishmania parasites are known to dampen host adaptive immunity by some unknown mechanisms (few known),which is a major lacuna in determining markers of vaccine induced immunity.Hence,to understand the parameters of protective immunity more studies such as induced effector properties of T cells and mechanisms associated with T cells multi-functionality are still required.During recent years various self immune inhibitory mechanisms have been explored,which control exacerbated immune response of the host to prevent self-damage.These mechanisms not only control the effectors function of immune cells but also reprogram them for their alternate functions such as humoral immunity and tissue remodeling to recover damage and maintain homeostasis between immune response (IR) and immune tolerance (IT),The mechanisms of immune suppression are broadly controlled by cytokines production that is mediated by molecules like PD1,CTLA4,CD200,CD200R,and CD300 etc.These molecules delivers inhibitory signals via immunoreceptor tyrosine based inhibitory motifs (ITIMs) & non ITIMs motifs after ligands interaction.Herein,we present the role of CD2200-CD200R immune inhibitory axis on CD4+ T Cell multi-functionality in Leishmania donovani infection.