EARLY INTRATHYMIC PRECURSOR CELLS ACQUIRE A CD4(LOW) PHENOTYPE

CD4(low) cells are a population of lymphoid lineage-restricted progeni tor cells representing the earliest precursors present in the adult th ymus, Paradoxically, thymic progenitors with a similar phenotype in fe tal mice and adult RAG-2-deficient (RAG-2(-/-)) mice lack this charact eristic low-level expression of CD4. We now show that radiation-induce d differentiation of CD4(+)CD8(+) double positive thymocytes in RAG-2( -/-) mice results in the appearance of low levels of CD4 on thymocytes that are phenotypically identical to CD4(low) progenitor cells presen t in the normal adult thymus. This suggests that CD4 surface expressio n can be passively transferred from double positive cells to early pro genitor thymocytes, Analysis of mixed bone marrow chimeras, reconstitu ted with hematopoietic stem cells from both CD4(-/-) (CD45.2) and CD4( wt) (CD45.1) congenic mice, revealed a CD4(low) phenotype on cells der ived from CD4(-/-) bone marrow cells. Furthermore, these CD4(-/-)-deri ved ''CD4(low)'' progenitors mere capable of reconstituting lymphocyte -depleted fetal thymi, with all thymocytes displaying a CD4(-/-) pheno type. This directly demonstrates that genetically CD4-deficient thymic progenitor cells can passively acquire a CD4(low) phenotype. Moreover , CD4 expression on CD4(low) progenitor thymocytes is sensitive to mil d acid treatment, indicating that CD4 may not exist as an integral cel l surface molecule on this thymocyte population. Our findings demonstr ate that low-level CD4 surface expression can be passively acquired by intrathymic progenitor cells from the surrounding thymic microenviron ment, suggesting that other cell surface molecules expressed at low le vels may also result from an acquired phenotype.