Do thymically and strictly extrathymically developing T cells generate similar immune responses?
If present in sufficient numbers, could extrathymic T cells substitute for thymus-derived T cells? To address this issue, we studied extrathymic T cells that develop in athymic mice under the influence of oncostatin M (OM). In this model, extensive T-cell development is probably due to amplification of a minor pathway of T-cell differentiation taking place only in the lymph nodes. Extrathymic CD4 T cells expanded poorly and were deficient in providing B-cell help after infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV). Compared with classic T cells, stimulated extrathymic CD8 T cells produced copious amounts of interferon gamma (IFN-gamma), and their expansion was precocious but of limited amplitude because of a high apoptosis rate. Consequently, although extrathymic cytotoxic T lymphocytes (CTLs) responded to LCMV infection, as evidenced by the expansion of GP33-41 tetramer-positive CD8 T cells, they were unable to eradicate the virus. Our data indicate that the site of development impinges on T-cell quality and function and that extrathymic T cells functionally cannot substitute for classical thymic T cells.
Blais
Marie-Eve
ME
Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada.
Gérard
Gwladys
G
Martinic
Marianne M
MM
Roy-Proulx
Guillaume
G
Zinkernagel
Rolf M
RM
Perreault
Claude
C
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D066298:In Vitro Techniques; D008211:Lymphocyte Cooperation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics; D018353:Rhabdoviridae Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D000914:Antibodies, Viral; C508352:Osm protein, mouse; D010455:Peptides; D053683:Oncostatin M