Regulation of CD45 isoforms during human effector and memory CD8 T cell differentiation: Implications for T cell nomenclature

CD45RA expression correlated closely with reduced expression of the splicing mediator hnRNP LL. This CD45RO to RA switch happens around one month post-infection and coincides with clearance of YFV, so we hypothesized that antigen may be playing a role in which CD45 isoform is expressed by the virus specific CD8 T cells. We addressed this issue by ex vivo analysis and provide evidence that this switch is indeed regulated by antigen.

Sorted CD45RO positive YFV specific effector CD8 T cells re-express CD45RA when cultured ex vivo in the absence of antigen. We then show that SARS-CoV-2 spike specific CD8 T cells undergo the same CD45RA to RO to RA transition in vivo in a longitudinal analysis of a cohort of COVID-19 patients receiving the SARS-CoV-2 mRNA vaccine. These studies have important implications for T cell nomenclature and in particular for defining human memory CD8 T cell subsets.

The re-expression of CD45RA in CD8 T cells likely explains the large number of TEMRA and absence of CM CD8 T cells. However, comparison to CD4 populations suggests that these findings are only applicable to CD8 T cells.