Abstract
Thymic epithelial cells (TEC), as part of thymic stroma, provide essential growth factors/cytokines and self-antigens to support T cell development and selection. Deletion of Rb family proteins in adult thymic stroma leads to T cell hyperplasia in vivo. To determine whether deletion of Rb specifically in keratin (K) 18 positive TEC was sufficient for thymocyte hyperplasia, we conditionally inactivated Rb and its family members p107 and p130 in K18+ TEC in genetically engineered mice (TgK18GT121; K18 mice). We found that thymocyte hyperproliferation was induced in mice with Rb inactivation in K18+ TEC, while normal T cell development was maintained; suggesting that inactivation of Rb specifically in K18+ TEC was sufficient and responsible for the phenotype. Transplantation of wild type bone marrow cells into mice with Rb inactivation in K18+ TEC resulted in donor T lymphocyte hyperplasia confirming the non-cell autonomous requirement for Rb proteins in K18+ TEC in regulating T cell proliferation. Our data suggests that thymic epithelial cells play an important role in regulating lymphoid proliferation and thymus size.
MeSH terms
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Animals
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Cell Proliferation*
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Female
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Gene Expression
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Keratin-18 / metabolism*
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Male
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Mice
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Mice, Transgenic
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / physiology*
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Stromal Cells / metabolism
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology
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Thymus Gland / cytology*
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Transgenes
Substances
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Keratin-18
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Retinoblastoma Protein
Grants and funding
This work was supported in part with Federal funds from the Frederick National Laboratory for Cancer Research, NIH, under Contract HHSN261200800001E (
https://frederick.cancer.gov/), and in part with research funding from National Cancer Institute (NCI,
https://www.cancer.gov/), and NCI CA084314 and CA046283 (
https://www.cancer.gov/), DOD PC040619 (
http://www.defense.gov/), Prostate Cancer Foundation to TVD (
http://www.pcf.org/), and DOD PC050306 to YS (
http://www.defense.gov/). The funders including Frederick National Laboratory operated by Leidos Biomedical Research, Inc. had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsements by the US Government.