Cryptopatches and isolated lymphoid follicles: dynamic lymphoid tissues dispensable for the generation of intraepithelial lymphocytes.
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.
Pabst
Oliver
O
Institute of Immunology, Hannover Medical School, D-30625 Hannover, Germany.
Herbrand
Heike
H
Worbs
Tim
T
Friedrichsen
Michaela
M
Yan
Sheng
S
Hoffmann
Matthias W
MW
Körner
Heiner
H
Bernhardt
Günter
G
Pabst
Reinhard
R
Förster
Reinhold
R
D000818:Animals; D004848:Epithelium / Q000033:anatomy & histology / Q000276:immunology; D006801:Humans; D007421:Intestine, Small / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D008221:Lymphoid Tissue / Q000033:anatomy & histology* / Q000166:cytology / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000172:deficiency / Q000235:genetics; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D051381:Rats; D013045:Species Specificity; D013552:Swine
C505886:LTB protein, human; C505887:Ltb protein, mouse; C505888:Ltb protein, rat; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins