Chemically modified antigen-presenting cells induce T lymphocyte allospecific hyporesponsiveness.
We have investigated the interaction between murine T lymphocytes and allogeneic APC in an in vitro proliferative mixed leukocyte reaction. Our results demonstrate that freshly isolated potentially alloreactive murine splenic T lymphocytes, in primary culture, can be induced to develop a state of allospecific proliferative hyporesponsiveness in vitro by exposure to 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide-modified allogeneic APC, a method similar to that previously used to induce nonresponsiveness in murine Ag-specific self-MHC-restricted T lymphocyte clones. This hyporesponsiveness was: specific for the allohaplotype of inducing APC, maintained for 96 h in vitro, not due to cellular inhibitory mechanisms, and associated with reduced ability to secrete IL-2 but not IL-3. Induction of this hyporesponsiveness was not due to altered expression of class II MHC gene products on the APC but was associated with markedly reduced T lymphocyte-APC adhesive interactions despite the lack of a detectable immunophenotypic change in lymphocyte function-associated Ag 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) expression on the modified APC. Therefore, we propose that TCR occupancy in the absence of normal T lymphocyte-APC adhesive clustering may induce T lymphocyte tolerance.
Ibrahim
M A
MA
Department of Histopathology, University College and Middlesex School of Medicine, London.
Coode
W K
WK
Takei
F
F
Ellis
J S
JS
Chain
B M
BM
Katz
D R
DR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005022:Ethyldimethylaminopropyl Carbodiimide / Q000031:analogs & derivatives / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; C041829:1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide methiodide; D005022:Ethyldimethylaminopropyl Carbodiimide