ANTIGEN-DEPENDENT SELECTION OF T-CELLS THAT ARE ABLE TO EFFICIENTLY REGULATE FREE CYTOPLASMIC CA2+ LEVELS

In T helper cells, the process of memory acquisition is reflected in t he expression of phenotypic markers. However, little is known regardin g the functional changes that occurred in T helper cells selected afte r a primary Ag-specific response. We now present data that indicate th at such T helper cells acquire the ability to down-regulate high conce ntrations of free cytoplasmic Ca2+. This property renders them resista nt to intense inductive stimuli, such as high concentrations of ionomy cin. The accumulation of cells that display this ability parallels the progressive proliferative enrichment of Ag-specife T cells and correl ates with the surface expression of the CD45RB(low) isoform. As previo usly shown, persistent high levels of cytoplasmic Ca2+ are responsible for death via apoptosis in virgin T cells. In contrast, the ability t o regulate cytosolic Ca2+ allows survival and clonal expansion. We sug gest that memory T cells behave differently from virgin T cells when i nteracting with Ag-presenting B cells (as reported by others) because they have acquired this new physiologic property. Ag-presenting B cell s deliver an intense stimulatory signal to T cells because of a high m ultiplicity of cognate interactions. Thus, Ag-driven T cell proliferat ion results in the selection of ''resistant'' T helper cells that can be successfully stimulated by memory B cells. in contrast, naive T cel ls, which cannot modulate high levels of cytosolic Ca2+ are deleted as a consequence of Ag presentation by B cells.