| Abstract: |
During intrathymic negative selection by clonal deletion, crosslinking of the T cell receptor (TCR) induces cell death by delivering an apoptotic signal(s) to the nucleus along a calcium-dependent pathway. We investigated the reactivity of early precursor-containing thymocytes to Ca2+-induced signals, and discovered a breakpoint in their sensitivity to calcium-mediated cell death (CMCD). CD25+ CD8−4− TCK− (triple negative [TN]) thymocytes stimulated with a calcium ionophore maintain their viability and precursor activity. By contrast, their immediate progeny, CD25−CD8lo4loTCRαβlo (triple low [TL]) cells react to calcium elevation by abrogation of precursor activity and apoptotic cell death. This developmental difference is specific for CMCD, since both CD25+ TN and CD25-TL cells are susceptible to steroid-induced apoptosis. The presence of bcl-2 mRNA correlates directly to the resistance to CMCD- CD25+ TN cells express it and CD25-TL cells do not. These experiments show that thymocytes become sensitive to Ca 2+-induced apoptosis as soon as they begin to express molecules that mediate thymic sdection, and suggest that a concomitant downregulation of bcl-2 may mediate this phenomenon. © 1993, Rockefeller University Press., All rights reserved. |
| Keywords: |
controlled study; proto-oncogene proteins; nonhuman; polymerase chain reaction; cd8 antigen; antigen expression; t-lymphocytes; animal cell; mouse; animal; mice; cell viability; cells, cultured; apoptosis; gene expression; cell maturation; calcium; mice, inbred balb c; mice, inbred c57bl; mice, inbred strains; t lymphocyte receptor; molecular sequence data; receptors, antigen, t-cell; thymus gland; rna, messenger; base sequence; down regulation; t-lymphocyte subsets; cd4 antigen; dna primers; antigens, cd4; proto-oncogene proteins c-bcl-2; calcium cell level; antigens, cd8; proto-oncogenes; protein-tyrosine kinase; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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