Functional CD8+ but not CD4+ T cell responses develop independent of thymic epithelial MHC.
The role of nonthymic epithelial (non-TE) MHC in T cell repertoire selection remains controversial. To analyze the relative roles of thymic epithelial (TE) and non-TE MHC in T cell repertoire selection, we have generated tetraparental aggregation chimeras (B6-nude<=>BALB/c and B6<=>BALB/c-nude) harboring T and B cells from both parents, whereas TE cells originated exclusively from the non-nude donor. These chimeras mounted protective virus-specific TE and non-TE MHC-restricted T cell responses. To further evaluate whether non-TE MHC alone was sufficient to generate a functional T cell repertoire, we generated tetraparental aggregation chimeras lacking MHC class II (B6-nude<=>MHCII(-/-)) or both MHC molecules (B6-nude<=>MHCI(-/-)II(-/-)) on TE cells, but not on cells of B6-nude origin. Chimeras with MHC-deficient TE cells mounted functional virus-specific CD8+ but not CD4+ T cell responses. Thus, maturation of functional CD4+ T cell responses required MHC class II on thymic epithelium, whereas CD8+ T cells matured in the absence of TE MHC.
Martinic
Marianne M
MM
Institute of Experimental Immunology, University Hospital Zurich, CH-8091 Zurich, Switzerland. marmar@liai.org
van den Broek
Maries F
MF
Rülicke
Thomas
T
Huber
Christoph
C
Odermatt
Bernhard
B
Reith
Walter
W
Horvath
Edit
E
Zellweger
Raphael
R
Fink
Katja
K
Recher
Mike
M
Eschli
Bruno
B
Hengartner
Hans
H
Zinkernagel
Rolf M
RM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013950:Thymus Gland / Q000276:immunology*; D014780:Viruses / Q000276:immunology
D000949:Histocompatibility Antigens Class II