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Significance Development of secondary lymphoid organs (SLO) was shown in mice to depend on lymphoid tissue inducer cells (LTi). Mutations of the IL2RG/JAK3 genes lead to severe combined immunodeficiency (SCID) characterized by an absence of T cells, natural killer cells, innate lymphoid cells, and likely LTi lymphocytes. Development of SLO was evaluated in T cell–reconstituted SCID patients by MRI, showing that lymph nodes were not detectable with the exception of those draining the gut. Analysis of tissues from a patient who died despite T cell reconstitution showed that lymph nodes were absent and that no LTi cells could be seen in the lymphoid-rich spleen and appendix. Thus, a LTi-independent pathway, mostly associated with the gut, contributes to SLO formation.

Alternative pathways for the development of lymphoid structures in humans