Modes of the initiation of T cell-mediated immune responses

Abstract

T cell-mediated immune response is the center of adaptive immunity. Despite more than five decades of research, the knowledge of mechanisms drives the initiation of T cell-mediated immune response is still limited due to the complexity of T cell-mediated immunity. Based on the accumulating evidences of Th1-mediated immune response, a "priming-activation" model was proposed to describe the initiation of the immune response. In this model, naïve CD4 T cells undergo a priming phase in the draining lymph nodes (dLNs) to polarize to Th1 fate by signals from dendritic cells (DCs). The primed Th1 cells then migrate to the antigen-affected loci and encounter antigen presenting cells (APCs) again. With signals from these cells, the primed Th1 cells differentiate to activated effector cells to coordinate Th1-centered immunity, which is the activation phase of Th1-mediated immune response. Recently, a model for the initiation of Th2-mediated immunity has been proposed, which highly resembles the priming-activation model for Th1 cells. We summarize the advances of Th17-mediated immunity and our understanding of it, and propose a two-step model for the initiation of Th17-mediated autoimmune immunity. Our model is similar to the priming-activation model of Th1 cells, as well. Although there are major knowledge gaps on molecular and cellular mechanisms in our model to be addressed, we hope that this model, with the associated gaps being addressed, will provide framework for research on the initiation of Th17-mediated immune responses and eventually enhances our understanding of how T cell-mediated immunity initiates.

Keywords: Th1; Th17; Th2; T cell-mediated immunity; priming-activation.

Figure 1:

A priming-activation model for the initiation of autoimmune type 3 immunity. (A) In the pathogenesis of EAE, naïve CD4 T cells are primed by DCs in the dLNs. The primed Th17 cells, npTh17, then migrate to CNS and differentiate to pTh17 cells. (B) A summary of molecular and cellular events in priming and activation of Th17 cells. Question marks indicate major knowledge gaps. DCs, dendritic cells; dLNs, draining lymph node; CNS, central nervous system. EAE, experimental autoimmune encephalomyelitis; APCs, antigen presenting cells.