Nasopharyngeal tonsils (adenoids) contain extrathymic corticothymocytes

Abstract

Adenoidal tissue (also known as nasopharyngeal tonsils) of 58% of humans in the pediatric age group contains immature T-lymphoid cells with the phenotype of thymocytes (TdT+, CD1abc+, cytoplasmic CD3+, coexpressing CD4 and CD8, lacking an Intraepithelial Lymphocyte-associated phenotype). The notable difference in comparison to palatine tonsils is the clustering in groups and sheets, comprising hundreds or thousands of cells (1.7%±0.2 of total T cells). The thymic epithelium is morphologically and phenotypically absent. Adenoids share with tonsils and lymph nodes the presence of immature B cell precursors (TdT+, CD1a-, Pax5+, Surrogate light chain±), however in these latter the presence of TdT+, CD1a+, Pax5- precursors is absent or limited to individual cells. Human adenoids are distinct among the Waldeyer's ring lymphoid tissue because of the known embryogenic derivation from the third pharyngeal pouch, from which the thymus develops; in addition, they may display phenotypic incomplete features of a vestigial thymus.

Figure 1. Phenotype and distribution of immature T cells in adenoids and tonsils.

A: macroscopic appearance of a representative sample of tonsils and adenoidal tissue. B: Low power (4x) image of a fixed and embedded adenoid, stained with Hematoxylin and Eosin. The brackets highlights the boundary between the stroma and the secondary lymphoid tissue (star  =  germinal center) where darker staining small lymphocytes gather. Left lower corner inset shows TdT+(brown) cells in sheets in an immunostained serial section (4x). Upper right inset: H&E detail of the bracketed area (40x). C-H: frozen adenoid serial sections (4x) stained for CD1a (C), CD1b (D), TE-7 (E), NGFR/p75 (F), and the anti thymic epithelium reagents RFD4 (G) and TE-4 (H) (brown, no counterstain). The insets in C, E and F show a magnified detail of the area occupied by immature T cells (40x)(also indicated by brackets). Star  =  germinal center. The insets in G and H show low power images (4x). The arrows highlight positive surface epithelium. I: frozen adenoid serial sections (40x) double stained for negative controls, TdT and CD1a, CD4, CD8, CD79a and surrogate light chain (SL; inset). Note the doublestaining in the upper half field, except for CD79a and SL. The last image is a double immunofluorescence image showing largely mutually exclusive distribution of Pax5 and TdT in adenoids in a fixed and embedded section. K: fixed and embedded tonsil section showing coexpression of TdT and Pax5 in immature B cell precursors.

Figure 2. Phenotype of TdT+ cells in adenoids, tonsils and secondary lymphoid organs.

A: Adenoid and tonsil from the same individual, stained by flow cytometry for surface antigens, show in the adenoid only CD1a+, surface CD3-, double CD4 and CD8 positive immature T cells. The tonsil is devoid of such cells. The numbers indicate the percentage in each gate. CD2+ T cells were enriched by SRBC rosetting. B: The phenotype of TdT+ cells in 12 tonsils, 10 adenoids and 20 lymph nodes is plotted. Each marker has been counted on TdT+ cells and the mean ± SD is shown. The variability is due to dilution with TdT+ immature B cells. An asterisk marks analysis not done. Note the unique presence of CD1a+ immature T cells in adenoids.