Extrathymic derivation of gut lymphocytes in parabiotic mice

In adult mice, c-kit(+) stem cells have recently been found in their liver, intestine and appendix, where extrathymic T cells are generated. A major p opulation of such thymus-independent subsets among intraepithelial lymphocy tes is T-cell receptor (TCR)gamma delta(+) CD4(-) CD8 alpha alpha(+)(beta(- )) cells, but the origins of other lymphocyte subsets are still controversi al. In this study, we examined what type of lymphocyte subsets were produce d in situ by such stem cells in the small intestine, large intestine and ap pendix. To investigate this subject, we used parabiotic B6.Ly5.1 and B5.Ly5 .2 mice which shared the same circulation by day 3. The origin of lymphocyt es was identified by anti-Ly5.1 and anti-Ly5.2 monoclonal antibodies in con junction with immunofluorescence tests. Lymphocytes in Peyer's patches and lamina propria lymphocytes (especially B cells and CD4(+) T cells) in the s mall intestine became a half-and-half mixture of Ly5.1(+) and Ly5.2(+) cell s in each individual of parabiotic pairs of mice by day 14. However, the mi xture was low in CD8 alpha alpha(+), CD8 alpha beta(+) and gamma delta T ce lls in the small and large intestines and in CD3(+) CD8(+) B220(+) cells in the appendix. These cells might be of the in situ origin. When one individ ual of a pair was irradiated before parabiosis, the mixture of partner cell s was accelerated. However, a low-mixture group, always continued to show a lower mixture pattern than did a high-mixture group. The present results s uggest that extrathymic T cells in the digestive tract may arise from their own pre-existing precursor cells and remain longer at the corresponding si tes.