Antigen presentation by epithelial cells induces anergic immunoregulatory CD45RO+ T cells and deletion of CD45RA+ T cells.
The immunoregulatory effects of alloantigen presentation by tissue parenchymal cells to resting peripheral blood CD4+ T cells was investigated. Coculture of CD45RO+ (memory) and CD45RA+ (naive) T lymphocytes with primary cultures of MHC class II-expressing epithelial cells rendered both populations of T cells hyporesponsive to a subsequent challenge by the same MHC molecule expressed on EBV-transformed lymphoblastoid B cell lines. However, the mechanisms responsible for the allospecific hyporesponsiveness were distinct. For the CD45RO+ T cells, responsiveness was restored by subsequent culture in the presence of IL-2; the addition of IL-2 had no effect on the reactivity of the CD45RA+ T cells. In contrast, the naive T cells were protected from the induction of nonresponsiveness by the presence of a neutralizing anti-CD95 Ab during the culture with thyroid follicular cells. In addition, the hyporesponsive CD45RO+ T cells effected linked suppression, in that they inhibited proliferation against a third-party DR alloantigen when the third-party alloantigen was coexpressed with the DR Ag against which hyporesponsiveness had been induced. These results suggest that recognition of Ag by T cells on tissue parenchymal cells plays an important role in the maintenance of peripheral T cell tolerance, inducing nonresponsiveness in naive and memory T cells by distinct mechanisms.
Marelli-Berg
F M
FM
Department of Immunology, Royal Postgraduate Medical School, London, United Kingdom.
Weetman
A
A
Frasca
L
L
Deacock
S J
SJ
Imami
N
N
Lombardi
G
G
Lechler
R I
RI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects; D017637:Clonal Deletion / Q000187:drug effects; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects / Q000276:immunology; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013961:Thyroid Gland / Q000166:cytology; D019014:fas Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007519:Isoantigens; D011994:Recombinant Proteins; D019014:fas Receptor; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens