Interconversion of CD45R subsets of CD4 T cells in vivo

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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 antibodies2,5– 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 reactions9,10 and interleukin-2 related activities5,6, whereas the CD45RO+ subset responds in vitro to recall antigens5,11 and provides help for antibody synthesis5,9. 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 cells8,11–13 is difficult to reconcile with this finding.

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