Cryptopatches and isolated lymphoid follicles: dynamic lymphoid tissues dispensable for the generation of intraepithelial lymphocytes

TLDR

Gut‑associated lymphoid tissues such as isolated lymphoid follicles and cryptopatches are less studied than secondary lymphoid organs. The study aimed to clarify how these structures organize and function, given their proposed roles in immune responses and extrathymic T‑cell development. Researchers examined size and cellular composition of small‑intestinal lymphoid aggregations in C57BL/6, BALB/c, and lymphotoxin‑deficient mice using flow cytometry, histology, and automated multi‑color immunofluorescence microscopy across large intestinal regions. The analyses revealed that intestinal lymphoid aggregations are highly variable in size and composition, often not fitting classic cryptopatch or isolated lymphoid follicle definitions, differ by species, age, and strain, allow rapid B‑cell but not T‑cell exchange in transplantation, and are absent in lymphotoxin‑deficient mice yet do not affect intraepithelial lymphocyte generation, demonstrating their dynamic plasticity and dispensability for IEL formation.

Abstract

Abstract In comparison to secondary lymphoid organs, gut‐associated lymphoid tissues such as isolated lymphoid follicles (ILF) and cryptopatches (CP) have been less intensively studied. To gain a better insight into processes regulating organization and function of these structures, which are believed to participate in immune responses and extrathymic T cell development, we characterized the lymphoid structures of the murine small intestine in more detail. The size and cellular composition of small intestinal lymphoid aggregations were analyzed in C57BL/6 and BALB/c wild‐type and lymphotoxin (LT)‐deficient mice, by flow cytometry, histology and automated multi‐color immunofluorescence microscopy evaluating large coherent areas of the intestine. These evaluations demonstrate that aggregated lymphoid structures in the small intestine vary in size and cellular composition, with a majority of structures not matching the current definitions of CP or ILF. Accordingly, significant variations depending on species, age and mouse strain were observed. Furthermore, small bowel transplantation revealed a rapid exchange of B but not T cells between host and grafted tissue. Moreover, LT‐deficient animals lack any intestinal lymphoid aggregations yet possess the complete panel of intraepithelial lymphocytes (IEL). In summary, our observations disclose intestinal lymphoid aggregations as dynamic structures with a great deal of inborn plasticity and demonstrate their dispensability for the generation of IEL.