Figure 4. Model for the induction of organogenesis of NALT and Peyer's patches by two subsets of CD3⁻CD4⁺CD45⁺ inducer cells.

CD3⁻CD4⁺CD45⁺ cells differentiate from fetal-liver progenitors. We propose that both ROR-γ (retinoic-acid-receptor-related orphan receptor-γ) and ID2 (inhibitor of DNA binding 2) are essential for the generation of interleukin-7 receptor (IL-7R)-expressing CD3⁻CD4⁺CD45⁺ cells for the induction of Peyer's-patch organogenesis. By contrast, the generation of the IL-7R⁻CD3⁻CD4⁺CD45⁺ inducer cells that are involved in nasopharynx-associated lymphoid tissue (NALT) organogenesis is regulated by ID2 but not ROR-γ. However, this model remains to be tested experimentally, and other possibilities exist (see main text). NALT genesis in ID2-deficient mice can be initiated by the adoptive transfer of CD3⁻CD4⁺CD45⁺ cells from wild-type mice, but the maturation of NALT formation is incomplete. This indicates that other cell populations, or the endogenous expression of ID2 at the site of NALT, might be required for the full maturation of NALT.