Interleukin‐2 receptor common γ‐chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: Selective induction of anti‐apoptotic (bcl‐2, bcl‐x_L) but not pro‐apoptotic (bax, bcl‐x_S) gene expression

Abstract

Cytokine deprivation from activated T cells leads to apoptosis associated with down-regulation of the bcl-2 gene product. It is not clear, however, how cytokines other than interleukin-2 (IL-2) may affect this process and regulate the involvement of other apoptosis-modulating genes. We show that a group of cytokines including IL-2 (IL-2R gamma), prevent the apoptosis of IL-2-deprived activated T cells. This rescue involves the induction of the anti-apoptosis genes bcl-2 and bcl-xL), but causes little change in expression of bax and bcl-xS, which promote apoptosis. Furthermore, the prevention of apoptosis and induction of proliferation by the common gamma chain cytokines can be dissociated. Thus, when proliferation is blocked, the common gamma chain cytokines still induce up-regulation of bcl-2 relative to bax and retard apoptosis. These cytokines can thus regulate the persistence or removal of effector T cells by coordinating the balance between genes which promote and those which inhibit apoptosis, events which are probably mediated at least in part by signals through the common gamma chain. These data also implicate inappropriate T cell apoptosis resulting from a dysfunctional common gamma-chain as part of the pathophysiological defect in patients with X-linked severe-combined immunodeficiency (SCID).

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer

“…Alternatively, it implies that activated T reg in the patients' circulation undergo a rapid turnover. The observed increased binding of Anx V by T reg is consistent with this hypothesis and with previous reports indicating that CD4 þ CD25 þ T cells are more susceptible to apoptosis than other CD4 þ T cells (Salmon et al, 1994;Akbar et al, 1996;Taams et al, 2001). Such rapid turnover of T reg in patients with SCCHN and other cancers (i.e., entry from the naïve pool, maturation and migration into tissues) explains their enrichment in lymphoid and tumour tissues, and the phenotype of T reg remaining in the circulation.…”

Apoptosis in the development of the immune system

“…In addition to promoting maturation, these cytokines function to promote survival by regulating members of the BCL-2 family. [33][34][35][36] This is best illustrated by the ability of BCL-2 overexpression to facilitate the development of mature T-cells (but strikingly not B-cells) in mice deficient for the IL-7 receptor or the gc. [37][38][39] Figure 3 Apoptosis and survival during thymic development.…”

The pathophysiology of photosensitivity in lupus erythematosus

“…Delayed apoptosis requires several hours for execution and is protein synthesis dependent. This can be the result of DNA damage (80) or due to lack of essential survival signals (81)(82)(83)(84).…”