Molecular Evidence for a Thymus-Independent Partial T Cell Development in a FOXN1−/− Athymic Human Fetus

Anna Fusco,Luigi Panico,Rosa Romano,Roberta D’Assante,Gabriella Bianchino,Giulia Scalia,Marisa Gorrese,Luigi Del Vecchio,Maria V Barone,Claudio Pignata,Loredana Palamaro,Vitina Grieco,Laura Vitiello,Eric Vivier

doi:10.1371/journal.pone.0081786

Abstract

The thymus is the primary organ able to support T cell ontogeny, abrogated in FOXN1−/− human athymia. Although evidence indicates that in animal models T lymphocytes may differentiate at extrathymic sites, whether this process is really thymus-independent has still to be clarified. In an athymic FOXN1−/− fetus, in which we previously described a total blockage of CD4+ and partial blockage of CD8+ cell development, we investigated whether intestine could play a role as extrathymic site of T-lymphopoiesis in humans. We document the presence of few extrathymically developed T lymphocytes and the presence in the intestine of CD3+ and CD8+, but not of CD4+ cells, a few of them exhibiting a CD45RA+ naïve phenotype. The expression of CD3εεpTα, RAG1 and RAG2 transcripts in the intestine and TCR gene rearrangement was also documented, thus indicating that in humans the partial T cell ontogeny occurring at extrathymic sites is a thymus- and FOXN1-independent process.

Highlights

The thymus supports a proper T cell ontogeny due to the presence of specialized epithelial cells, resulting in the export of naıve CD45RA+ CD62L+ T cells that follows the recruitment of progenitors from bone marrow [1]
Evidence indicates that T cells may differentiate at extrathymic sites, as intestine and liver [2,3,4,5,6], where T cell populations may arise from preexisting precursor cells [7,8], even though it still remains to be demonstrated if the process is fully thymus-independent
We previously described that in the FOXN12/2 CBMCs, most of the CD8+ cells were CD32 [25], we looked at the CD8aa+ cells on CD32 gated lymphocytes

Summary

Introduction

The thymus supports a proper T cell ontogeny due to the presence of specialized epithelial cells, resulting in the export of naıve CD45RA+ CD62L+ T cells that follows the recruitment of progenitors from bone marrow [1].Evidence indicates that T cells may differentiate at extrathymic sites, as intestine and liver [2,3,4,5,6], where T cell populations may arise from preexisting precursor cells [7,8], even though it still remains to be demonstrated if the process is fully thymus-independent. The quantitative PCR analysis revealed that the amount of this molecule in the intestine of FOXN12/2 fetus was even higher than in the control (Figure 2F).

Results

Conclusion