1993 Fiscal Year Final Research Report Summary
Analysis of the mechanism of negative and positive selection in the thymus : Use of CD4^+8^+ lymphoma cells as a model system
| Project/Area Number |
04670294
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Keio University |
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Principal Investigator |
TADAKUMA Takushi Associate Professor Department of Microbiology, Keio University School of Medicine, 医学部, 助教授 (30051626)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Formation of T cell repertoire / Negative selection / Positive selection / CD4^+8^+ lymphoma / Apoptosis |
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| Research Abstract |
T cells are responsible for the discrimination of self and non-self. To acquire such activities, however, T cells must encounter two selections in the thymus, namely negative and positive selections. For analysis of the mechanism of these two selections, development of in vitro experimental systems is inevitable. We established CD4^+8^+ lymphomas transformed with radiation leukemia virus, and the following results were obtained.
(1)Lymphomas express either V beta 6 TcR or V beta 6/V beta TcR, and apoptosis is inducible in these cells when stimulated with anti-CD3 or anti-TcR antibodies, cortisone, Ca ionophores, cAMP, etc.
(2)The cells expressing V beta 8 TcR are susceptible to the inhibition of proliferation and apoptosis in the presence of Staphylococcus enterotoxin B(SEB) and antigen presenting cells (APC). The subsequent experiments revealed that B cells, dendritic cells and epithelial cells are effective as APC if they express class II antigens on the cell surface. Furthermore, I-E encoded class II antigens are found mainly used for antigen presentation, and anti-CD4 antibody could suppress the induction of apoptosis.
(3)The cells that escaped from cell death turned out to be CD4^+8^- cells. To accompany this change, various other changes were observed including the reduced expression of HSA antigens, the increased expression of H-2 antigens and the acquisition of the ability of IL-2L/IL-4 production when stimulated with phorbol ester plus Ca ionophore.
(4)Cyclosporin A could block both the induction of apoptosis and the acquisition of the ability of IL-2/IL-4 production, but did not influence the transition from CD4^+8^+ to CD4^+8^- phenotype. Various changes are induced by the signals via the same TcR, but our results suggest that different signal pathways may be used in these changes.
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