Characterizing the T-cell survival and differentiation during priming with downregulated γ-c cytokine/Jak3 signals (50.34)

Abstract

Abstract T-cells play a central role in cell mediated immune responses to foreign antigens. Optimal T-cell activation and expansion requires antigen recognition via cognate T-cell receptors (TCRs) along with co-stimulatory and cytokine signals. The cytokine signals that lead to T-cell activation and proliferation, involve binding of common gamma-chain cytokines to their cognate receptors, that in turn activates Janus tyrosine kinase (Jak) 3, inducing cytokine gene transcription via the Jak/Stat (Signal Transducers and Activators of Transcription) pathway. However, it is currently unknown as to whether these paradigms of signaling during T-cell priming are universal to all T-cell subsets and lineages or unique to each. In the current study, we have examined the role of γ-c cytokine/Jak3 axis of signaling in survival and differentiation of different T-cell subsets during early phases of priming. We show highly reduced survival of CD8+ T-cells under cytokine/Jak3 inhibiting conditions during activation, whereas CD4+ T-cells were fairly more resistant. Loss of Jak3 signaling also inhibited the Treg differentiation while promoting pro-inflammatory Th17 cells thus, suggesting discrete and specific roles of this signaling pathway in different T-cell subsets and lineages. These findings contribute to our understanding of T-cell activation in different T-cell lineages as well as their differentiation into subsets, and are important for designing therapeutic approaches of the immune responses.