Immune Netw.  2004 Jun;4(2):81-87. 10.4110/in.2004.4.2.81.

Antigen Nonspecific Death of Immature Thymocytes by Corticosteroids and TNF

• Oh K
• Surh CD
• Cho J
• Lee DS

• KMID: 1637946
• DOI: http://doi.org/10.4110/in.2004.4.2.81

Abstract

BACKGROUND
In the thymus, developing thymocytes continually interact with thymic epithelial cell components. Self MHC restriction of mature T cells are imposed in the thymus through interaction of immature double positive thymocytes and thymic cortical epithelial cells. The site of negative selection, however, is a matter of debate. Through systemic injection of anti-TCR antibody or antigenic peptides, investigators suggested that most of the negative selection occurs in the thymic cortex. But the requirements for negative selection, i.e cellular counterparts and costimulatory molecules are more available in the medulla or cortico-medullary junction rather than in the thymic cortex. METHODS: The direct and indirect pathways of thymocyte death after systemic anti-TCR antibody injection were separated through several experimental systems. B6 mice were either adrenalectomized or sham-adrenalectomized to evaluate the role of endogenous glucocorticoids from adrenal gland. Role of TNF were evaluated through using TNF receptor double knockout mice. RESULTS: We found that without indirectly acting mediators such as TNF-alpha or corticosteroid, double positive thymocyte death were minimal by systemic injection of anti-TCR antibody in TNF receptor double knockout neonatal mice. Also by analyzing neonatal wild-type mice with adoptively transferred mature T cells, only peripheral activation of mature T cells could induce extensive double positive thymocyte death. CONCLUSION: Thus, systemically injected anti-TCR antibody mediated thymocyte death are mostly induced through indirect pathway.

Keyword

Thymocyte death; negative selection; TNF; corticosteroid

MeSH Terms

Adrenal Cortex Hormones*
Adrenal Glands
Animals
Epithelial Cells
Glucocorticoids
Humans
Mice
Mice, Knockout
Peptides
Receptors, Tumor Necrosis Factor
Research Personnel
T-Lymphocytes
Thymocytes*
Thymus Gland
Tumor Necrosis Factor-alpha
Adrenal Cortex Hormones
Glucocorticoids
Peptides
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha