Fratricide: a mechanism for T memory-cell homeostasis

Immunological memory depends on a self-renewing pool of antigen-specific T memory (Tm) cells but the homeostatic mechanisms that maintain the size and diversity of the pool are largely unknown. Competition for space or growth factors has been suggested as a mechanism but how these factors themselves are regulated is unclear. We suggest that Tm-cell fratricide by Fas-mediated apoptosis results in a density-dependent death rate that controls the size of the pool without requiring competition for resources or an external quorum-sensing mechanism. A mathematical model based on this concept predicts the known behaviour of the Tm pool, including observed differences in heterogeneity of the CD4 and CD8 compartments and might provide a paradigm for homeostasis of other haematopoietic-cell populations.