International Immunology, Vol. 2, No. 8, pp. 755-763,August 1990
© 1990 Japanese Society for Immunology
T cell clones are killed by a thymic stromal cell monolayer following stamulation of T cell receptor with antigen and/or H-2 molecules on the monolayer
Biomedical Research Center, Osaka University Medical School Osaka 553, Japan
1 Tokyo University School of Medicine Tokyo 113, Japan
2 Chiba University School of Medicine Chiba 280, Japan
3 Saga Medical School Saga 840-01, Japan
4 National Institute of Radiological Sciences Chiba 260, Japan
5 The Third Department of Anatomy, Osaka University Medical School Osaka 553, Japan
Correspondence to: Correspondence to: Dr H. Fjiwara, Biomedical Research Center, Osaka University Medical School, 1-1-50 Fukushima-ku, Osaka 553, Japan
A thymic stromal cell clone, MRL104.8a, expressed class I and class II H-2k antigens after exposure to 
-interferon (-IFN) and produced thymic stroma-derived T cell growth factor (TSTGF) irrespective of -IFN exposure. Culturing the keyhole limpet hemocyanin (KLH)-specif I-Ek-restricted 9–16 helper T cell (Th) clone on an Ia (I-Ak and I-Ek)-expressing MRL104.8a monolayer induced potent proliferation of the 9–16 cells by virtue of the TSTGF produced by the monolayer. In contrast, the addition of KLH to cultures resulted in lethal growth inhibition of the 9–16 Th clone. Such a phenomenon was also observed for various Th as well as cytotoxic T lymphocyte (CTL) clones, and the following were revealed: (I) the growth of the ovalbumin (OVA)- or bovine thyroglobulin (BTg)-specific Th clone on the la-expressing MRL104.8a monolayer was also inhibited by addition of the relevant antigen. The fact that these Th clones required antigen-presenting cells (APC) capable of processing antigen for the recognition of the respective target antigen suggested the potential of MRL104.8a cells for antigen-processing; (ii) the lethal growth inhibition of KLH-specific, I-Ak (23–1–8)- or I-Ek (9–16)-restricted Th clone was prevented selectively by anti-I-Ak or anti-I-Ek antibody respectively; (III) the I-Ek-alloreactive Th clone (2–13) was supported for its growth on a -IFN-unexposed MRL104.8a monolayer, whereas this clone was killed on an I-Ek-expressing monolayer; and (iv) when I-Ak-reactive CTL clones were cultured on an Ia– or la+ monolayer, CTL clones failed to exhibit cytotoxic effect on either the Ia– or the la+ monolayer, but were conversely killed by the la+ monolayer. Its killing was also prevented by an antibody which inhibits the recognition of Ia antigen on the monolayer by CTL clones. These results indicate that a specialized thymic stromal cell clone supports the growth of various T cell clones but has a lethal effect on these T cell clones when their T cell receptor is stimulated with the corresponding antigen and/or H-2 molecules expressed on the stromal cell.
Keywords: thymic stromal cells, thymic selection, T cell death, la expression
Received 19 March 1990, accepted 24 May 1990.