Normal peripheral T-cell function in c-Fos-deficient mice.

Abstract

The ubiquitous transcription factors Fos and Jun are rapidly induced in T cells stimulated through the T-cell antigen receptor and regulate transcription of cytokines, including interleukin 2, in activated T cells. Since positive and negative selection of thymocytes during T-cell development also depends on activation through the T-cell receptor, Fos and Jun may play a role in thymocyte development as well. Fos and Jun act at several regulatory elements in the interleukin 2 promoter, including the AP-1 and NFAT sites. Using antisera specific to individual Fos and Jun family members, we show that c-Fos as well as other Fos family members are present in the inducible AP-1 and NFAT complexes of activated murine T cells. Nevertheless, c-Fos is not absolutely required for the development or function of peripheral T cells, as shown by using mice in which both copies of the c-fos gene were disrupted by targeted mutagenesis. c-Fos-deficient mice were comparable to wild-type mice in their patterns of thymocyte development and in the ability of their peripheral T cells to proliferate and produce several cytokines in response to T-cell receptor stimulation. Our results suggest that other Fos family members may be capable of substituting functionally for c-Fos during T-cell development and cytokine gene transcription in activated T cells.

Comparison of naïve and central memory derived CD8+effector cell engraftment fitness and function following adoptive transfer

“…2D). [21][22][23] In line with these findings, intracellular phosphorylated AKT (pAKT), an effector molecule of co-stimulatory receptors such as CD28, 24 was present in higher abundance in CD8 C T CM derived CTLs than in CD8 C T N/SCM derived CTLs (Fig. 2E, F) and the mRNA encoding the apoptosis facilitator BCL2L11 was 13-fold lower in T CM derived CTLs than that of T N/SCM derived CTLs.…”

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

“…Inactivation of IkB results in enhanced granulopoiesis (Beg et al, 1995a), possibly caused by increased or constitutive expression of cytokines such as GM ± CSF. Gene disruption of c-jun in mice appears to have no e ect upon T cell proliferation or activation , but c-fos activation results in dramatically reduced numbers of certain T cell sub-sets (Johnson et al, 1992;Wang et al, 1992), although these results are not supported by others (Jain et al, 1994). Similarly to ETS1 gene inactivation, these experiments have accentuated the importance of NFkB and AP1 in the events of T cell activation, although there may be some redundancy in function between the di erent AP1 family members.…”

Stable IL-2 Decision Making by Endogenous c-Fos Amounts in Peripheral Memory T-helper Cells

“…These mice revealed only a slightly decreased IL-2 expression compared with wild type mice (14). In the light of our data and data from c-Fos transgenic mice showing enhanced IL-2 production (17), we speculate that other Fos proteins might substitute for c-Fos in the c-Fos knock-out mice.…”