Predicting CD62L expression during the CD8+ T-cell response in vivo

Acute infection leads to CD8(+) T-cell activation, division and differentiation. Following clearance of infection, cells revert to two distinct subsets of memory, central (T-CM) and effector (T-EM) memory. Adoptive transfer of naive T-cell receptor transgenic (TCR-tg) T cells has been used to study the differentiation of these memory subsets, which are often discriminated by expression of CD62L. Naive CD8(+) T cells are CD62L(high), and CD62L expression is lost during the 'effector' phase. Adoptive transfer studies show that higher transfer frequencies result in diminished T-cell expansion and a higher proportion CD62L(high). This suggests a relationship between CD62L expression and cell division, where division leads to conversion from CD62L(high) to CD62L(low) phenotype. To address this hypothesis we adoptively transferred graded numbers of OT-1 TCR-tg T cells from naive donors and tracked the kinetics and phenotype of the immune response after infection. We developed a simple mathematical model of division-linked CD62L differentiation, which we compared with the experimental data. Our results show that division-linked differentiation predicts the differences in proportion of cells CD62L(high) observed between responses of different adoptive transfer number and within individual mice. We calculate that approximately 20% of CD62L(high) cells convert to CD62L(low) during each division. Immunology and Cell Biology (2010) 88, 157-164; doi:10.1038/icb.2009.80; published online 27 October 2009