T-cell regeneration after bone marrow transplantation: Differential CD45 isoform expression on thymic-derived versus thymic-independent progeny

To study the source of regenerated T cells after bone marrow transplantation (BMT), lethally irradiated thymectomized and thymus-bearing C57BL/6 (Thy 1.2⁺) mice were injected with syngeneic T-cell depleted bone marrow (TCD BM) cells and graded numbers of congenic B6/Thy 1.1⁺ lymph node (LN) cells. LN cell expansion was the predominant source for T-cell regeneration in thymectomized hosts but was minimal in thymus-bearing hosts. Analysis of T-cell receptor (TCR) expression on LN progeny showed a diverse Vβ repertoire. Therefore, peripheral T-cell progenitors exist within Vβ families, but expansion of these progenitors after BMT is downregulated in the presence of a functional thymus. CD4⁺ cells derived from BM versus LN in thymus-bearing hosts displayed differential CD44 and CD45 isoform expression. BM-derived cells were primarily CD45RB⁺ CD44lo and LN derived cells were nearly exclusively CD45RB^- CD44hi. In thymectomized hosts, BM, host, and LN CD4⁺ progeny were CD45RB^- CD44hi. We conclude that T-cell regeneration via peripheral T-cell progenitors predominates in hosts lacking thymic function and gives rise to T cells that display a 'memory' phenotype. In contrast, the ability to generate sizable populations of 'naive' type T cells after BMT appears limited to the prethymic progenitor pool and could serve as a marker for thymic regenerative capacity.