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

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Abstract
Acute infection leads to CD8+ T‐cell activation, division and differentiation. Following clearance of infection, cells revert to two distinct subsets of memory, central (TCM) and effector (TEM) 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 CD62Lhigh, 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 CD62Lhigh. This suggests a relationship between CD62L expression and cell division, where division leads to conversion from CD62Lhigh to CD62Llow 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 CD62Lhigh observed between responses of different adoptive transfer number and within individual mice. We calculate that approximately 20% of CD62Lhigh cells convert to CD62Llow during each division.