Peripheral engraftment of fetal intestine into athymic mice sponsors t cell development

Direct evidence for thymopoietic function of murine small intestine

R Lee Mosley, John R. Klein

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Adult athymic, lethally irradiated, F1 → parent bone marrow-reconstituted (AT × BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment. Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts. As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT × BM-SHAM) were essentially void of T cells, whereas in AT × BM thymus-engrafted (AT × BMTHG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT × BM fetal intestine-engrafted (AT × BM-FIG) mice beginning 3 wk postengraftment. Based on H-2 expression, peripheral T cells in AT × BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-α/β+ T cells with both CD4+8 and CD48+ subsets. Peripheral T cells in AT × BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3e. Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT × BM-FIG and AT × BMTHG mice, though not in spleen cell cultures from AT × BM-SHAM mice. Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that thymus leukemia (T4 antigens were expressed on epithelial surfaces ofintestine grafts, and that both TCR-α/β+ and TCR-γ/δ+ lymphocytes were present in intestine grafts. Collectively, these findings indicate that the murine small intestine has the capacity to initiate and regulate T cell development from bone marrow precursors, thus providing a mechanism by which extrathymic development of intestine lymphocytes occur.

Original languageEnglish (US)
Pages (from-to)1365-1373
Number of pages9
JournalJournal of Experimental Medicine
Volume176
Issue number5
DOIs
StatePublished - Nov 1 1992

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Nude Mice
Small Intestine
Intestines
T-Lymphocytes
Spleen
Thymus Gland
T-Cell Antigen Receptor
Lymphocytes
Transplants
Lymph Nodes
Bone Marrow
Cell Culture Techniques
Cytotoxic T-Lymphocytes
Capsules
Fluorescent Antibody Technique
Staining and Labeling
Kidney

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Peripheral engraftment of fetal intestine into athymic mice sponsors t cell development: Direct evidence for thymopoietic function of murine small intestine",
abstract = "Adult athymic, lethally irradiated, F1 → parent bone marrow-reconstituted (AT × BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment. Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts. As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT × BM-SHAM) were essentially void of T cells, whereas in AT × BM thymus-engrafted (AT × BMTHG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT × BM fetal intestine-engrafted (AT × BM-FIG) mice beginning 3 wk postengraftment. Based on H-2 expression, peripheral T cells in AT × BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-α/β+ T cells with both CD4+8− and CD4−8+ subsets. Peripheral T cells in AT × BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3e. Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT × BM-FIG and AT × BMTHG mice, though not in spleen cell cultures from AT × BM-SHAM mice. Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that thymus leukemia (T4 antigens were expressed on epithelial surfaces ofintestine grafts, and that both TCR-α/β+ and TCR-γ/δ+ lymphocytes were present in intestine grafts. Collectively, these findings indicate that the murine small intestine has the capacity to initiate and regulate T cell development from bone marrow precursors, thus providing a mechanism by which extrathymic development of intestine lymphocytes occur.",
author = "Mosley, {R Lee} and Klein, {John R.}",
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T1 - Peripheral engraftment of fetal intestine into athymic mice sponsors t cell development

T2 - Direct evidence for thymopoietic function of murine small intestine

AU - Mosley, R Lee

AU - Klein, John R.

PY - 1992/11/1

Y1 - 1992/11/1

N2 - Adult athymic, lethally irradiated, F1 → parent bone marrow-reconstituted (AT × BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment. Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts. As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT × BM-SHAM) were essentially void of T cells, whereas in AT × BM thymus-engrafted (AT × BMTHG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT × BM fetal intestine-engrafted (AT × BM-FIG) mice beginning 3 wk postengraftment. Based on H-2 expression, peripheral T cells in AT × BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-α/β+ T cells with both CD4+8− and CD4−8+ subsets. Peripheral T cells in AT × BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3e. Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT × BM-FIG and AT × BMTHG mice, though not in spleen cell cultures from AT × BM-SHAM mice. Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that thymus leukemia (T4 antigens were expressed on epithelial surfaces ofintestine grafts, and that both TCR-α/β+ and TCR-γ/δ+ lymphocytes were present in intestine grafts. Collectively, these findings indicate that the murine small intestine has the capacity to initiate and regulate T cell development from bone marrow precursors, thus providing a mechanism by which extrathymic development of intestine lymphocytes occur.

AB - Adult athymic, lethally irradiated, F1 → parent bone marrow-reconstituted (AT × BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment. Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts. As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT × BM-SHAM) were essentially void of T cells, whereas in AT × BM thymus-engrafted (AT × BMTHG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT × BM fetal intestine-engrafted (AT × BM-FIG) mice beginning 3 wk postengraftment. Based on H-2 expression, peripheral T cells in AT × BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-α/β+ T cells with both CD4+8− and CD4−8+ subsets. Peripheral T cells in AT × BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3e. Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT × BM-FIG and AT × BMTHG mice, though not in spleen cell cultures from AT × BM-SHAM mice. Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that thymus leukemia (T4 antigens were expressed on epithelial surfaces ofintestine grafts, and that both TCR-α/β+ and TCR-γ/δ+ lymphocytes were present in intestine grafts. Collectively, these findings indicate that the murine small intestine has the capacity to initiate and regulate T cell development from bone marrow precursors, thus providing a mechanism by which extrathymic development of intestine lymphocytes occur.

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