We identified CD8(+)CD122(+) regulatory T cells (Tregs) and demonstrated their importance in the maintenance of immune homeostasis and in the recovery from experimental autoimmune encephalomyelitis. In this paper, we show that CD8(+)CD122(+) Tregs effectively prevent and cure colitis in a mouse model. In our experiments, colitis was induced in lymphocyte-deficient RAG-2(-/-) mice by transferring CD4(+)CD45RB(high) cells that were excluded with CD4(+) Tregs. Cotransfer of CD8(+)CD122(+) cells clearly suppressed the development of colitis, and this suppressive effect was similar to that of CD4(+)CD45RB(low) cells that were mostly CD4(+) Tregs. CD8(+)CD122(+) cells obtained from IL-10(-/-) mice were unable to suppress colitis, indicating that IL-10 is an important effect-transmitting factor in the suppression of colitis. CD8(+)CD122(+) cells showed a suppressive effect when they were transferred 4 wk after CD4(+)CD45RB(high) cells, indicating the therapeutic potential of CD8(+)CD122(+) cells. A mixture of CD8(+)CD122(+) cells and CD4(+)CD45RB(low) cells was far more effective than single Tregs, indicating the synergistic effect of these Tregs. These overall findings demonstrate the potential role of CD8(+) Tregs, and possibly together with CD4(+) Tregs, in the medical care of inflammatory bowel disease patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4049/jimmunol.1000800 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The High-Affinity IL-2 Receptor Affects White Matter Damage after Cerebral Ischemia by Regulating CD8 + T Lymphocyte Differentiation.
J Neuroimmune Pharmacol
January 2025
Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
IL-2/IL-2R inhibition improved the prognosis of ischemic stroke by regulating T cells, while the respective contribution of T cells with high/medium/low-affinity IL-2 receptors remained unclear. Single-cell RNA sequencing data of ischemic brain tissue revealed that most of the high-affinity IL-2R would be expressed by CD8 + T cells, especially by a highly-proliferative subset. Interestingly, only the CD8 + T cells with high-affinity IL-2R infiltrated ischemic brain tissues, highly expressing 32 genes (including Cdc20, Cdca3/5, and Asns) and activating 7 signaling pathways (including the interferon-alpha response pathway, a key mediator in the proliferation, migration, and cytotoxicity of CD8 + T cells).
View Article and Find Full Text PDFECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation.
Cell Rep
January 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Electronic address:
Proteasomes generate antigenic peptides presented on cell surfaces-a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-antigens is crucial to suppress encephalitogenic T cell responses by elevating regulatory T (Treg) cell populations.
View Article and Find Full Text PDFAge-Dependent Bi-Phasic Dynamics of Ly49CD8 Regulatory T Cell Population.
Aging Cell
December 2024
Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4Foxp3 regulatory T cells (Tregs) have been well documented.
View Article and Find Full Text PDFIL-2/anti-IL-2 antibody complexes augment immune responses to therapeutic cancer vaccines.
Proc Natl Acad Sci U S A
November 2024
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
One driver of the high failure rates of clinical trials for therapeutic cancer vaccines is likely the inability to sufficiently engage conventional dendritic cells (cDCs), the antigen-presenting cell (APC) subset that is specialized in priming antitumor T cells. Here, we demonstrate that, relative to vaccination with an injectable mesoporous silica rod (MPS) vaccine alone (Vax), combining MPS vaccines with CD122-biased IL-2/anti-IL-2 antibody complexes (IL-2cx) drives ~3-fold expansion of cDCs at the vaccination sites, vaccine-draining lymph nodes, and spleens of treated mice. Furthermore, relative to Vax alone, Vax+IL-2cx led to a ~3-fold increase in the numbers of CD8 T cells and ~15-fold increase in the numbers of NK cells at the vaccination site.
View Article and Find Full Text PDFHuman serum albumin promotes interactions between HSA-IL-2 fusion protein and CD122 for enhancing immunotherapy.
Biomed Pharmacother
December 2024
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China; Li Song's Academician Workstation of Hainan University (School of Pharmaceutical Sciences), Hainan University, Sanya 572000, China. Electronic address:
Interleukin 2 (IL-2) is a multifunctional cytokine that is crucial for T-lymphocytes proliferation and differentiation. However, IL-2 binds to IL-2Rα (CD25) subunit preferentially and tends to stimulate regulatory T cells (Tregs), which express high-affinity trimeric receptors (IL-2Rαβγ), resulting in immunosuppressive effects. Therefore, development of methods that enhance IL-2/CD122 interactions and activate immune responses without affecting therapeutic efficacy of IL-2 may be desirable.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!