Thus, this model may have limited value for the study of rectal transmission of HIV. Two other studies showed successful rectal infections BET bromodomain inhibitor of humanized mice (4, 37), with transmission rates of 6/7 and 11/14, respectively. Sun et al. (37) used NOD/SCID mice transplanted with fetal liver and thymus and later reconstituted with liver-derived CD34+ cells (BLT mice). Berges et al. (4) transplanted RAG2?/?��c?/? mice with CD34+ cells from fetal liver. Thus, a major difference is that we used cord blood-derived cells. So far, it is not clear which source of hematopoietic stem cells is optimal for the generation of humanized mice. In vitro, the colony-forming efficiency of CD34+ cells derived from fetal liver is higher than that of cord blood CD34+ cells (19).

However, in vivo cord blood-derived hematopoietic stem cells produced four times more mature human leukocytes than liver-derived cells, when the same number of stem cells was transplanted into adult NOD/SCID mice (18). When telomere length is used as a measure of replicative capacity of hematopoietic stem cells from fetal liver and cord blood, the differences are minimal (40), indicating that both are suitable for generating humanized mice. However, it is not known to what extent the origin of lymphoid cells may be critical for repopulation of the intestines with human cells. Different expression of cell adhesion molecules (30) could influence homing behavior and subsequent repopulation of lymphoid organs. That, in turn, may explain the lower infection rates we observed in our model using cord blood-derived cells for transplantation.

But when we reconstituted mice in parallel either with cord blood-derived or with fetal liver-derived cells, rectal transmission of HIV was not more efficient in the mice which had received liver-derived cells. Apart from the different origins of CD34+ cells, Berges et al. and we used similar models based on mice with the same genetic background. However, Berges et al. reported higher engraftment levels than the ones we detected. They found blood engraftment levels of almost 90%, whereas the mice used in our study had a mean engraftment of about 11%. But these values cannot be directly compared. Berges et al. measured the percentage of human cells in blood lymphocytes; we measured the percentage of human cells in all blood leukocytes, which include murine cells as well.

Since RAG2?/?��c?/? mice have no B, T, and NK cells of their own, obviously Batimastat all lymphocytes detected in humanized mice should be of human origin. In our cohort of mice transplanted with liver-derived cells, we saw no differences in engraftment levels compared to engraftment levels in littermates transplanted with cord blood-derived cells. This indicates that the origin of the stem cells probably has no major impact, at least in our hands, and that other factors are influencing HIV transmission rates in humanized mice.