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

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 naïve 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. Naïve 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 naïve donors and tracked the kinetics and phenotype of the immune response following infection. We developed a simple mathematical model of division-linked CD62L differentiation which we compared to 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.