Premium
Control of thymus‐independent intestinal intraepithelial lymphocytes by β2‐microglobulin
Author(s) -
Neuhaus Oliver,
Emoto Masashi,
Blum Carmen,
Yamamoto Shigeki,
Kaufmann Stefan H. E.
Publication year - 1995
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830250832
Subject(s) - t cell receptor , intraepithelial lymphocyte , biology , cd8 , mhc class i , major histocompatibility complex , immunology , microbiology and biotechnology , t cell , antigen , immune system
Abstract Murine intestinal intraepithelial lymphocytes (i‐IEL) comprise thymusdependent cells such as T cell receptor (TcR) α/β CD8α/β + i‐IEL, as well as thymus‐independent ones such as TcRα/β CD8α/α + and TcRγ/δ CD8α/α + i‐IEL. Whilst the development of the CD8α/β expressing i‐IEL is strictly contingent on major histocompatibility complex (MHC) class I surface expression, that of CD8α/α i‐IEL appears largely MHC class I independent. We have used β2‐microglobulin (β2m) −/− mutant mice lacking surface‐expressed MHC class I and TcRα/β CD8α/β + i‐IEL to analyze the potential impact of MHC class I on regional activation of thymus‐independent i‐IEL. To analyze the role of TcRγ/δ i‐IEL in regional cell interactions, these mice were treated with the anti‐TcRγ/δ mAb, GL3. Whilst numbers of TcRα/β CD8α/α i‐IEL were markedly reduced in βm +/− mice, those of TcRγ/δ i‐IEL were elevated. Administration of GL3 in vivo caused TcR down‐modulation and functional inactivation of TcRγ/δ i‐IEL in β2m +/− mice. In contrast, TcR expression and functional activities of TcRγ/δ i‐IEL from β2m −/− mice were not impaired by GL3 treatment. The TcRα/β CD8β i‐IEL from β2m −/− mice were expanded and functionally activated as a consequence of TcRγ/δ engagement. The TcRγ/δ i‐IEL and TcRα/β CD8α/α + i‐IEL from athymic nu / nu mice which express MHC class I, but lack TcRα/β CD8α/β + i‐IEL, responded to TcRγ/δ engagement as those from the β2m +/− controls. In addition, the TcRγ/δ i‐IEL from TcRβ −/− and TcRβ +/− mutants were equally affected by GL3. We conclude that the absence of β2m renders TcRγ/δ i‐IEL resistant to TcR‐mediated inactivation and promotes activation of TcRα/β CD8β − i‐IEL. The activation of TcRγ/δ i‐IEL seems to be directly controlled by β2m/MHC class I expression and independent from TcRα/β CD8β + i‐IEL. Regulation of self‐reactive thymus‐independent i‐IEL through β2m/MHC class I may contribute to control of autoreactive immune responses in the intestine.