TY - JOUR
T1 - Immunological consequences of T cell-specific expression of H-2Kb molecules in transgenic mice
AU - Simpson, S. J.
AU - Tomlinson, P.
AU - Mellor, A. L.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 1993/2
Y1 - 1993/2
N2 - CBA (H-2k) mice carrying a H-2Kb transgene (CD2Kb) linked to transcriptional control elements from the human CD2 gene express H-2Kb at high levels on all thymocytes and peripheral T cells. However, skin grafts from two independent transgenic lineages, CD2Kb-2 and CD2Kb-3, are not rejected by recipient CBA mice. Although mice from both lineages tolerate H-2Kb disparate skin grafts, tolerance is maintained by different mechanisms because H-2Kb-specific cytotoxic T cells cannot be generated in vitro using CD2Kb-2 responder spleen cells, but can be generated when responder cells are from CD2Kb-3 mice. Furthermore, H-2Kb-restricted cytotoxic T cell responses directed against minor histocompatlbillty antigens can be obtained from CD2Kb-2 responder mice. Thus, negative and positive selection of immature thymocytes seems to take place in CD2Kb-2 mice, even though the pattern of H-2Kb expression is modified by the CD2Kb transgene. In contrast, H-2Kb-specific cytotoxic T cell precursors are not eliminated in CD2Kb-3 mice, even though all thymocytes express H-2Kb in these mice. However, these potentially autoreactive H-2Kb-specific T cells are apparently inactive in vivo and fail to lyse syngeneic CD2Kb-3 target cells in vitro, even when activated to lyse other H-2Kb-expressing cells. These results reveal that tolerance in CD2Kb-3 mice is induced either by a non-deletional mechanism or by partial elimination of a subset of cytotoxlc T cell precursors capable of recognizing H-2Kb as a target antigen.
AB - CBA (H-2k) mice carrying a H-2Kb transgene (CD2Kb) linked to transcriptional control elements from the human CD2 gene express H-2Kb at high levels on all thymocytes and peripheral T cells. However, skin grafts from two independent transgenic lineages, CD2Kb-2 and CD2Kb-3, are not rejected by recipient CBA mice. Although mice from both lineages tolerate H-2Kb disparate skin grafts, tolerance is maintained by different mechanisms because H-2Kb-specific cytotoxic T cells cannot be generated in vitro using CD2Kb-2 responder spleen cells, but can be generated when responder cells are from CD2Kb-3 mice. Furthermore, H-2Kb-restricted cytotoxic T cell responses directed against minor histocompatlbillty antigens can be obtained from CD2Kb-2 responder mice. Thus, negative and positive selection of immature thymocytes seems to take place in CD2Kb-2 mice, even though the pattern of H-2Kb expression is modified by the CD2Kb transgene. In contrast, H-2Kb-specific cytotoxic T cell precursors are not eliminated in CD2Kb-3 mice, even though all thymocytes express H-2Kb in these mice. However, these potentially autoreactive H-2Kb-specific T cells are apparently inactive in vivo and fail to lyse syngeneic CD2Kb-3 target cells in vitro, even when activated to lyse other H-2Kb-expressing cells. These results reveal that tolerance in CD2Kb-3 mice is induced either by a non-deletional mechanism or by partial elimination of a subset of cytotoxlc T cell precursors capable of recognizing H-2Kb as a target antigen.
KW - Major histocompatibility complex
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=0027459410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027459410&partnerID=8YFLogxK
U2 - 10.1093/intimm/5.2.189
DO - 10.1093/intimm/5.2.189
M3 - Article
C2 - 8095799
AN - SCOPUS:0027459410
SN - 0953-8178
VL - 5
SP - 189
EP - 198
JO - International Immunology
JF - International Immunology
IS - 2
ER -