Interconversion of CD45R subsets of CD4 T cells in vivo

Abstract

TLYMPHOCYTES express multiple forms of the leukocyte common antigen CD45, transcribed by alternative usage of leukocyte-common antigen exons 4–6 (refs 1–4). Species-specific monoclonal antibodies^{2,5– 8} against restricted epitopes (CD45R) of the antigen subdivide CD4 T cells into reciprocal subsets expressing either the high molecular weight isoforms CD45RA or RB (ref. 4) or a molecule in which exons 4–6 have been spliced out (CD45RO)⁴. CD45R⁺ or RB⁺ CD4 T cells are potent in graft-versus-host reactions^9,10 and interleukin-2 related activities^5,6, whereas the CD45RO⁺ subset responds in vitro to recall antigens^5,11 and provides help for antibody synthesis^5,9. It is unclear whether CD45RO subsets derive from separate lineages, or are products of unidirectional or reversible differentiation. We show by transferring CD45R⁺ or CD45R⁻ allotype-marked CD4 T cells into athymic nude rats that both subsets routinely generate cells of the opposite phenotype with a function that follows phenotype, not parentage. The recent equation of CD45R subsets as maturation stages representing 'naive' and 'memory' T cells^8,11–13 is difficult to reconcile with this finding.