Molecular and cellular control of T1/T2 immunity at the interface between antimicrobial defense and immune pathology

The immune system evolved to rapidly recognize infectious threats and promptly mobilize cellular effectors to the infection site. Establishment of a robust T1-type immunity is a prerequisite for effective defense against most viruses and intracellular bacteria. However, accumulating evidence shows that T1 and T2 responses during such infections are not mutually exclusive. A possibility may be that the dual T1-T2 nature of antiviral immune responses is merely a byproduct of less than perfect crossregulatory mechanisms. Herein, we discuss molecular and cellular mechanisms of T-cell differentiation along with recent evidence supporting the hypothesis that rather than representing an epiphenomenon, coinduction of virus-specific T2 cells plays a significant homeostatic role. Thus, molecular pathways that regulate IL-4 production during influenza virus infection monitor T1-mediated immune responses in vital organs such as lungs and prevent immune pathology that may otherwise interfere with recovery from disease. Such evidence suggests that coinduction of T2 immunity maintains immune homeostasis during T1-mediated defense reactions. Finally, we outline implications on the earlier concept of T1/T2 dichotomy, supporting a model in which these two subsets, rather than being mutually antagonistic, together facilitate the recovery from infection.