CD4dull+ hematopoietic progenitor cells in murine bone marrow

Abstract

CD4+ cells comprise approximately 3% to 6% of murine bone marrow (BM) cells. The majority are CD4dull+, but there are two distinct sub populations: CD4 brightly positive Gr-1- cells (CD4hiGr-1-) and CD4+ Gr- 1+ cells (CD4loGr-1lo). CD4hiGr-1- cells are considered to be mature T cells by cell surface antigen expression and morphology. CD4loGr-1lo cells, which comprise approximately 0.6% of the BM cells, express small amount of B220 and Thy1 antigens. Interestingly, colony-forming units (CFU)-spleen and CFU-C are not enriched in this population. However, when injected into lethally irradiated mice, CD4loGr-1lo cells were shown to differentiate into T-cell, B-cell, and myelo-monocyte lineages when assayed 26 weeks after transplantation. Furthermore, donor-derived CD4loGr-1lo cells were present in the recipients' BM at least 16 weeks after transplantation. These observations suggest that murine CD4loGr- 1lo cells in BM have self-renewal capability and retain the ability to differentiate into at least three lineages in long-term hematopoiesis.

The expression and differentiation pattern of cell antigens and adhesion molecules on the nonadherent cell population in canine long‐term marrow culture: a biphasic development of myeloid and lymphoid cells

“…The function of CD4 antigen, which is expressed by mature helperlinducer T cells, thymocytes, monocytes, as well as by the small cell population in marrow and brain, is not clear CD4'" cells harvested from 10-day-old long-term marrow culture failed to grow in the clonal assay, but were able to grow in the long-term culture-initiating cell model, albeit with a five-fold lower potential as compared to CD34+ cells (data not shown). Our data are in agreement with the results obtained by Onishi et al (32).…”

“…However, the data obtained by Onishi et al a s well as our data support the view that there exists another type of hematopoietic stem cell that expresses low levels of lineage markers but is still capable of differentiating into multiple lineages in vivo or in vitro. This is in agreement with the view that CD4'" precursors are a heterogeneous population possibly including distinct precursors for each lineage, and that a clonal assay for these cells has not yet been established (32).…”

“…They have defined a novel population of cells in the marrow (CD4I0 Gr-l'O cells) that has an ability to reconstitute long-term hematopoiesis. CD41° Gr-ll" cells are distinct from hematopoietic stem cells previously defined as ThyLo Lin-in that they have low CFU-C and no CFU-S activity and that they express lineage markers for myeloid (Gr-I), T (CD4) and B @220) at a low level together with Thy1 (32). Pluripotent hematopoietic stem cells were previously believed to be contained within a population of cells that had low amounts of differentiation antigens or none at all (33).…”

Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation.

“…In our opinion, thymus c-kit cells are derived from BM c-kit cells and the CD41~ lymphoid progenitors found by Wu et al in the thymus could derive either from Lin-Thy-1 l~ Sca-1 + (2) or from Lin-Thy-11~ c-kit + (9) stem cells. Alternatively, low CD4 precursors may be derived from the CD4 l~ hema- topoietic stem cells in the bone marrow that we and others have reported (34)(35)(36) and which appear to be independent of the Lin-Thy-11~ stem cells. More precise analysis using multi-parameter cell sorting and organ culture, preferably at -~176 t a single cell level, should aid to clarify the chronological relationships among these cell populations.…”