Extrathymic derivation of gut lymphocytes in parabiotic mice

Abstract

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 population of such thymus-independent subsets among intraepithelial lymphocytes is T-cell receptor (TCR)gamma delta+ CD4- CD8alpha alpha+(beta-) cells, but the origins of other lymphocyte subsets are still controversial. In this study, we examined what type of lymphocyte subsets were produced in situ by such stem cells in the small intestine, large intestine and appendix. 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 lymphocytes was identified by anti-Ly5.1 and anti-Ly5.2 monoclonal antibodies in conjunction with immunofluorescence tests. Lymphocytes in Peyer's patches and lamina propria lymphocytes (especially B cells and CD4+ T cells) in the small intestine became a half-and-half mixture of Ly5.1+ and Ly5.2+ cells in each individual of parabiotic pairs of mice by day 14. However, the mixture was low in CD8alpha alpha+, CD8alpha beta+ and gamma delta T cells 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 individual of a pair was irradiated before parabiosis, the mixture of partner cells was accelerated. However, a low-mixture group always continued to show a lower mixture pattern than did a high-mixture group. The present results suggest that extrathymic T cells in the digestive tract may arise from their own pre-existing precursor cells and remain longer at the corresponding sites.

Intra- and Intercompartmental Movement of γδ T Cells: Intestinal Intraepithelial and Peripheral γδ T Cells Represent Exclusive Nonoverlapping Populations with Distinct Migration Characteristics

“…In this scenario, the highly motile and mobile peripheral gd T cells of the cotransplanted MLNs completely exchanged with their respective host counterparts during a period of 7 d. At the same time, the analysis of the transplanted intestines clearly showed that there was no redistribution of graft and host gd iIEL cells taking place. Of note, the use of TcrdH2BeGFP reporter mice allowed us to unambiguously identify bona fide gd T cells and revealed an even lower level of cellular exchange between donor and graft gd iIELs than expected from previous studies using parabiotic mice (59,60). Importantly, most probably due to their capacity of local selfrenewal, environmental niches for intestinal gd T cells were occupied in this experimental model.…”

Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int B220+ γδ T cells with double‐negative CD4– CD8– phenotype in the liver

“…[25][26][27] In the present study, for the first time, we found a large expansion of cd T cells with the phenotype DN CD4 -CD8 -and B220 + in DBA/2 mice after malarial infection. In addition to the DN phenotype, the expression of the B220 + B-cell marker on T cells was unique.…”

Immune Functioning in Non lymphoid Organs: The Liver

“…Extrathymic pathways of T cell differentiation exist in the intestine and liver (Sato et al 1995), where T cell populations may arise from their own preexisting precursor cells rather than thymus (Sugahara et al 1999). Extrathymic T cells are also present in the uterus and exocrine glands, for example, salivary gland (Abo 2001 (int) , and presence of self-reactive clones (Abo 1993;Ohteki et al 1992).…”