Donor cell persistence and activation-induced unresponsiveness of peripheral CD8+ T cells

Ehl, Stephan; Barchet, Winfried; Oehen, Stephan; Aichele, Peter; Hombach, Joachim; Hengartner, Hans; Zinkernagel, Rolf M.

doi:10.1002/1521-4141(200003)30:3<883::aid-immu883>3.0.co;2-u

Cited by 19 publications

(18 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to foreign immunogenic Ags, autoantigens, especially nuclear autoantigens, share the following properties: persistent and low-level expression on resting APCs, as suggested in other anergic models (55)(56)(57)(58)43). Fig.…”

Section: Discussionmentioning

confidence: 93%

“…ϩ T cell clones which were repeatedly stimulated by agonistic ligands were rendered anergic in vitro (58), and that anergy of CD8 ϩ T cells was induced and maintained by Ag persistence in vivo (56). Alternatively, repeated transfusion could eventually increase the amount of the self-peptide in vivo to a level which is sufficient to induce tolerance.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Peripheral Tolerance to a Nuclear Autoantigen: Dendritic Cells Expressing a Nuclear Autoantigen Lead to Persistent Anergic State of CD4+ Autoreactive T Cells After Proliferation

Kawahata

Misaki

Yamauchi

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

It remains unknown why the T cell tolerance to nuclear autoantigens is impaired in systemic autoimmune diseases. To clarify this, we generated transgenic mice expressing OVA mainly in the nuclei (Ld-nOVA mice). When CD4+ T cells from DO11.10 mice expressing a TCR specific for OVA323–339 were transferred into Ld-nOVA mice, they were rendered anergic, but persisted in vivo for at least 3 mo. These cells expressed CD44high, CD45RBlow, and were generated after multiple cell divisions, suggesting that anergy is not the result of insufficient proliferative stimuli. Whereas dendritic cells (DCs) from Ld-nOVA (DCs derived from transgenic mice (TgDCs)), which present rather low amount of the self-peptide, efficiently induced proliferation of DO11.10 T cells, divided T cells stimulated in vivo by TgDCs exhibited a lower memory response than T cells stimulated in vitro by peptide-pulsed DCs. Furthermore, we found that repeated transfer of either TgDCs or DCs derived from wild-type mice pulsed with a lower concentration of OVA323–339 induced a lower response of DO11.10 T cells in Ag-free wild-type recipients than DCs derived from wild-type mice. These results suggest that peripheral tolerance to a nuclear autoantigen is achieved by continuous presentation of the self-peptide by DCs, and that the low expression level of the peptide might also be involved in the induction of hyporesponsiveness.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Peripheral Tolerance to a Nuclear Autoantigen: Dendritic Cells Expressing a Nuclear Autoantigen Lead to Persistent Anergic State of CD4+ Autoreactive T Cells After Proliferation

Kawahata

Misaki

Yamauchi

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…These observations suggest that the fate of AINR CTL differs depending upon whether or not they continue to be exposed to Ag. Ehl et al (44) have similarly observed that CTL unresponsiveness can be a consequence of persistent Ag. Clearly, further study will be needed to understand the mechanisms that determine the ultimate fate of CTL following a primary response to Ag and the programmed development of AINR.…”

Section: Discussionmentioning

confidence: 97%

Activation-Induced Nonresponsiveness: A Th-Dependent Regulatory Checkpoint in the CTL Response

Tham

Shrikant

Mescher

2002

The Journal of Immunology

View full text Add to dashboard Cite

CD8 T cells undergo autocrine IL-2-dependent proliferation upon TCR engagement and costimulation, but within 3–4 days, they become activation-induced nonresponsive (AINR) and display a split anergy. They can lyse targets and secrete IFN-γ but they cannot produce IL-2 in response to TCR ligation and costimulation, due at least in part to an inability to up-regulate mitogen-activated protein kinases and IL-2 mRNA. Exogenous IL-2 can drive continued proliferation of AINR cells and nonresponsiveness is reversed within 1–2 days so that Ag-driven proliferation can resume. Mitogen-activated protein kinases and IL-2 mRNA can again be up-regulated, but “rewiring” has occurred so that these events no longer depend upon costimulation; TCR engagement is sufficient. Development of AINR appears to be a normal part of the differentiation program of CD8 T cells, providing a regulatory checkpoint to convert the initial helper-independent response to one that depends upon CD4 T cell help for continued expansion of the effector CTL. Once permission is given, in the form of IL-2, to pass this checkpoint, the CTL can make a prolonged response to persisting Ag in the absence of further CD4 T cell help.

show abstract

“…While recreating conditions of high-dose tolerance [40] those reports failed to address how B lymphocytes regulate CD8 T cells under non-physiological conditions. On the other hand, the injection of a low number of B lymphocytes expressing the H-Y minor histocompatibility antigen was shown to be immunogenic not tolerogenic [41].…”

Section: Discussionmentioning

confidence: 99%

CD8 T cell priming by B lymphocytes is CD4 help dependent

Castiglioni¹,

Gerloni²,

Cortez-Gonzalez³

et al. 2005

Eur J Immunol

View full text Add to dashboard Cite

While it is generally accepted that B lymphocytes can present antigen and activate CD4 T cells, priming of CD8 T cells by B lymphocytes remains controversial. Recently, we showed that mice injected with genetically programmed B lymphocytes generate antigen specific CD4 and CD8 T cell responses in vivo that could also be induced in mice lacking functional dendritic cells. To gain further insights into the requirements for T cell priming by antigen-presenting B lymphocytes, in vitro experiments were performed using ovalbumin (OVA) and OVA-specific TCR-transgenic CD4 and CD8 T cells. We found that while B lymphocytes can directly prime CD4 T cells, the activation of CD8 T cells requires T cell help. Transfer experiments show that help can either be contact dependent or be mediated by soluble factors in the supernatants of activated OVAspecific CD4 T cells. Furthermore, the effect of activated CD4 T cells can be replaced by soluble recombinant IL-4. Collectively, the data show the existence of different requirements for priming of CD4 and CD8 T cells and point to the previously unappreciated fact that the induction of CD8 T cell responses by B lymphocytes requires T cell help.

show abstract

Donor cell persistence and activation-induced unresponsiveness of peripheral CD8+ T cells

Cited by 19 publications

References 48 publications

Peripheral Tolerance to a Nuclear Autoantigen: Dendritic Cells Expressing a Nuclear Autoantigen Lead to Persistent Anergic State of CD4+ Autoreactive T Cells After Proliferation

Peripheral Tolerance to a Nuclear Autoantigen: Dendritic Cells Expressing a Nuclear Autoantigen Lead to Persistent Anergic State of CD4+ Autoreactive T Cells After Proliferation

Activation-Induced Nonresponsiveness: A Th-Dependent Regulatory Checkpoint in the CTL Response

CD8 T cell priming by B lymphocytes is CD4 help dependent

Contact Info

Product

Resources

About