Receptor-mediated Apoptosis in T Lymphocytes

The TNF Receptor Family Member CD30 Is Not Essential for Negative Selection

“…Dominant negative Nur77-transgenic mice exhibit partial defects of negative selection. In contrast, constitutive expression of Nur77 (Nur77-FL) leads to massive thymic apoptosis (22). During our efforts to further define the downstream targets for Nur77, we found that CD30 levels were elevated on thymocytes from Nur77FL mice compared with the wild-type littermates.…”

“…Our experiments with the CD30 Ϫ/Ϫ Nur77FL-transgenic mice have shown that CD30 is not involved in thymic apoptosis caused by Nur77 overexpression (22). In an effort to characterize CD30 further, we undertook a brief study of the CD30 Ϫ/Ϫ mice.…”

“…During our efforts to further define the downstream targets for Nur77, we found that CD30 levels were elevated on thymocytes from Nur77FL mice compared with the wild-type littermates. Subsequent analysis of Nur77-FL mice in CD30 Ϫ/Ϫ background, however, revealed that CD30 does not play a direct role in Nur77-mediated apoptosis in the thymus (22). To confirm the role of CD30 in negative selection, we examined the effect of CD30 mutation on apoptosis mediated by alloreactivity against I-A s in transgenic mice that express the cytochrome c/I-Especific TCR (23).…”

NR4A1 (nuclear receptor subfamily 4, group A, member 1)

“…Another apoptosis regulating protein, BAX, is thought to recruit NR4A1 into the mitochondria to mediate apoptosis (Wilson et al, 2003). NR4A1 further induces apoptosis by reacting with self-recognizing major histocompatibility complex molecules in T cell (Zhang et al, 1999). NR4A1 acts as an inflammatory factor in T-cell, and T-cell receptor-mediated apoptosis can be prevented by inhibiting NR4A1 function (Liu et al, 1994;Woronicz et al, 1994).…”

“…Thus, NR4A1 appear to be involved in cell growth and survival, but the detailed mechanisms are still largely unknown. Apoptosis Contradictory to its apparent role in cell survival, NR4A1 also activates several genes involved in cell apoptosis as well as translocating directly into mitochondria to enhance the apoptotic signal (Li et al, 2000;Lin et al, 2004;Zhang et al, 1999). For example, NR4A1 induces apoptosis in cultured prostate cancer cells through activation of the transcription factor E2F1 (Mu and Chang, 2003;Wilson et al, 2003).…”