Bystander CD4(+)T cells: crossroads between innate and adaptive immunity

Abstract

T cells are the central mediators of both humoral and cellular adaptive immune responses. Highly specific receptor-mediated clonal selection and expansion of T cells assure antigen-specific immunity. In addition, encounters with cognate antigens generate immunological memory, the capacity for long-term, antigen-specific immunity against previously encountered pathogens. However, T-cell receptor (TCR)-independent activation, termed "bystander activation", has also been found. Bystander-activated T cells can respond rapidly and secrete effector cytokines even in the absence of antigen stimulation. Recent studies have rehighlighted the importance of antigen-independent bystander activation of CD4(+)T cells in infection clearance and autoimmune pathogenesis, suggesting the existence of a distinct innate-like immunological function performed by conventional T cells. In this review, we discuss the inflammatory mediators that activate bystander CD4(+)T cells and the potential physiological roles of these cells during infection, autoimmunity, and cancer.

Immunology: bystander helper T cells in health and disease Immune cells that become activated in the absence of antigen stimulation could be harnessed in the fight against infection, autoimmunity, and cancer. Je-Min Choi and colleagues from Hanyang University in Seoul, South Korea, review how the immune system can deploy helper T cells through an unusual process called bystander activation. Most T cells become activated only after receptors on their surface bind to specific cognate antigen. In contrast, bystander T cells are activated non-specifically in response to cytokines and other pro-inflammatory mediators. Studies have shown that this cell population has a variety of protective and pathogenic functions, for example, guarding against multiple sclerosis, aggravating the symptoms of parasitic infections and promoting antitumor immunity. A better understanding of these immune cells could lead to new therapeutic options for these diseases.