Susceptibility to cell death is a dominant phenotype: triggering of activation-driven T-cell death independent of the T-cell antigen receptor complex.
The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant.
Nickas
G
G
Division of Immunology, Medical Biology Institute, La Jolla, California 92037.
Meyers
J
J
Hebshi
L D
LD
Ashwell
J D
JD
Gold
D P
DP
Sydora
B
B
Ucker
D S
DS
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D016923:Cell Death / Q000235:genetics*; D005799:Genes, Dominant; D007700:Kinetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D018800:Thy-1 Antigens; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development
D000950:Antigens, Ly; D000954:Antigens, Surface; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens