Model for clonal elimination in the thymus.
A thymic stromal cell clone, MRL104.8a, expresses class I as well as class II H-2k antigens after exposure to gamma-interferon. This clone also produces thymic stroma-derived T-cell growth factor (TSTGF), which is distinct from other known interleukins and is capable of promoting the growth of various antigen-specific helper T cell (Th) clones without requiring a specific antigen or interleukin 2. When the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted Th clone 9-16 was cultured on an Ia (I-Ak and I-Ek)-expressing MRL104.8a monolayer, potent proliferation of the 9-16 cells was induced by TSTGF produced by the monolayer. In contrast, the addition of KLH resulted in lethal growth inhibition of Th clone 9-16 cells. Another Th clone that is KLH-specific but I-Ab-restricted was capable of proliferating on the Iak-expressing MRL104.8a monolayer whether or not KLH was present. More importantly, death of Th clone 9-16 cells cultured on a MRL104.8a monolayer in the presence of KLH was almost completely prevented by the addition of anti-I-Ek or anti-CD3 monoclonal antibodies, which are capable of blocking antigen recognition by the T-cell receptor. However, when Th clone 9-16 cells were cultured in the presence of KLH but on a monolayer of MRL28.8a cells, another thymic stromal clone that expresses a comparable amount of I-Ek antigen but produces a marginal amount of TSTGF, cells did not die; a lethal effect was induced by adding TSTGF. These results indicate that the TSTGF-producing and Ia-expressing thymic stromal cells induce the continuous proliferation or selective elimination of each T-cell clone, depending on whether the T-cell receptor is stimulated by the relevant antigen associated with Ia molecules expressed on the stromal cell surface.
Kosaka
H
H
Biomedical Research Center, Osaka University Medical School, Japan.
Ogata
M
M
Hikita
I
I
Maruo
S
S
Sugihara
S
S
Matsubara
H
H
Takai
Y
Y
Hamaoka
T
T
Fujiwara
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells; D006133:Growth Substances / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell