CCR2 identifies first responders among human CD4+ memory T cells: long-lived, apoptosis-resistant, antigen-responsive cells with enhanced migration potential, a low threshold for activation, and immediate effector capabilities (85.5)

The persistence and roles of memory T cells with effector capability have been questioned. We analyzed human memory CD4+ T cells from peripheral blood defined by their expression of chemokine receptors CCR5 and CCR2, the principal subsets being CCR5−CCR2−, CCR5+CCR2−, and CCR5+CCR2+. CCR2+ cells co-expressed the most chemokine receptor types (up to six) and migrated to the greatest number of chemokines, followed by CCR5+CCR2− cells. Numbers of T cell receptor gene excision circles were CCR5−CCR2− > CCR5+CCR2− > CCR5+CCR2+. The CCR2+ cells were those most readily activated through TCR but showed reduced proliferative potential, were enriched in cells responding to a remote immunogen, secreted high levels of effector cytokines, and were resistant to apoptosis. By contrast, the CCR5+CCR2− population was enriched in recently activated/cycling cells and Treg, and was more susceptible to apoptosis. The data suggest that patterns of CCR5 and CCR2 expression separate effector- vs. memory-cell enriched CD4+ subsets, and that CCR2 marks highly differentiated, long-lived memory cells with effector capabilities. The data also suggest co-ordination among a memory cell’s position on a unidirectional pathway of differentiation, ability to be recruited into tissue, and threshold for activation/effector function, with the most chemokine-responsive cells being best equipped as first responders in a recall response.