Memory-Phenotype CD4+ T Lymphocytes: A Double-Edged Sword in Immune Responses

CD4 + T lymphocytes play an essential role in adaptive immune responses and comprise nave, effector, and memory compartments.In pathogen infection, foreign antigen (Ag)specific nave T lymphocytes are activated to give rise to effector and memory cells to contribute to host protection from the pathogen.In addition to the conventional activation pathway, accumulating evidence suggests that some nave cells can weakly respond to self-Ags to convert to "memory-phenotype (MP) cells" in steady state.Whereas newly generated MP cells adopt a rapidly proliferating, undifferentiated feature, they cease to divide with time while differentiating into distinct subsets including T helper type 1 (Th1)-like "MP1," T helper type 17 (Th17)-like "MP17," follicular helper T (Tfh)-like "MPfh," and regulatory T cells.Functionally, these MP subsets can exert innate and adaptive immune responses to contribute to infectious and anti-tumor immunity as well as autoimmunity, demonstrating both physiological and pathological aspects of MP T lymphocytes.Furthermore, recent reports suggest that self-reactive MP cells are also existent in humans.In this article, I will review our current understanding on generation, maintenance, differentiation, and immunological functions of MP CD4 + T lymphocytes and discuss their potential as a new therapeutic target in several disease contexts.