scholarly journals Enforced IL-10 Expression Confers Type 1 Regulatory T Cell (Tr1) Phenotype and Function to Human CD4+ T Cells

2012 ◽  
Vol 20 (9) ◽  
pp. 1778-1790 ◽  
Author(s):  
Grazia Andolfi ◽  
Georgia Fousteri ◽  
Maura Rossetti ◽  
Chiara F Magnani ◽  
Tatiana Jofra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Cd4 T Cells ◽  
And Function

scholarly journals Interleukin 2 Signaling Is Required for CD4+ Regulatory T Cell Function

2002 ◽  
Vol 196 (6) ◽  
pp. 851-857 ◽  
Author(s):  
Gláucia C. Furtado ◽  
Maria A. Curotto de Lafaille ◽  
Nino Kutchukhidze ◽  
Juan J. Lafaille
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Protective Function ◽  
And Function

Mice deficient in interleukin (IL)-2 production or the IL-2 receptor α or β chains develop a lethal autoimmune syndrome. CD4+ regulatory T cells have been shown to prevent autoimmune diseases, allograft rejection, and to down-regulate antibody responses against foreign antigens. To assess the role of IL-2 in the generation and function of regulatory T cells, we transferred CD4+ T cells from mice genetically deficient in IL-2 or IL-2Rα (CD25) expression. A small number of splenic or thymic CD4+ T cells from IL-2 knockout mice can protect mice from spontaneous experimental autoimmune encephalomyelitis (EAE). In contrast, splenic or thymic CD4+ T cells from CD25 knockout donor mice conferred little or no protection. We conclude that T cells with regulatory potential can develop, undergo thymic selection, and migrate to the peripheral lymphoid organs in the absence of IL-2, and do not protect from disease by means of IL-2 secretion. However, IL-2 signaling in regulatory T cells is essential for their protective function. Altogether, our results favor a model whereby IL-2 induces regulatory T cell activity.

scholarly journals Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors

2021 ◽  
Vol 12 ◽  
Author(s):  
Laurie G. Landry ◽  
Amanda M. Anderson ◽  
Holger A. Russ ◽  
Liping Yu ◽  
Sally C. Kent ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Cd4 T Cells ◽  
Pancreatic Beta Cells ◽  
Hot Spot ◽  
Cell Receptor ◽  
Organ Donors ◽  
Hla Dq

Proinsulin is an abundant protein that is selectively expressed by pancreatic beta cells and has been a focus for development of antigen-specific immunotherapies for type 1 diabetes (T1D). In this study, we sought to comprehensively evaluate reactivity to preproinsulin by CD4 T cells originally isolated from pancreatic islets of organ donors having T1D. We analyzed 187 T cell receptor (TCR) clonotypes expressed by CD4 T cells obtained from six T1D donors and determined their response to 99 truncated preproinsulin peptide pools, in the presence of autologous B cells. We identified 14 TCR clonotypes from four out of the six donors that responded to preproinsulin peptides. Epitopes were found across all of proinsulin (insulin B-chain, C-peptide, and A-chain) including four hot spot regions containing peptides commonly targeted by TCR clonotypes derived from multiple T1D donors. Of importance, these hot spots overlap with peptide regions to which CD4 T cell responses have previously been detected in the peripheral blood of T1D patients. The 14 TCR clonotypes recognized proinsulin peptides presented by various HLA class II molecules, but there was a trend for dominant restriction with HLA-DQ, especially T1D risk alleles DQ8, DQ2, and DQ8-trans. The characteristics of the tri-molecular complex including proinsulin peptide, HLA-DQ molecule, and TCR derived from CD4 T cells in islets, provides an essential basis for developing antigen-specific biomarkers as well as immunotherapies.

scholarly journals Generation of a Novel T Cell Specific Interleukin-1 Receptor Type 1 Conditional Knock Out Mouse Reveals Intrinsic Defects in Survival, Expansion and Cytokine Production of CD4 T Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0161505 ◽  
Author(s):  
Ilgiz A. Mufazalov ◽  
Tommy Regen ◽  
Carsten Schelmbauer ◽  
Janina Kuschmann ◽  
Alisa M. Muratova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Receptor Type ◽  
Intrinsic Defects ◽  
Knock Out ◽  
Knock Out Mouse

scholarly journals Immune checkpoint expression on HIV-specific CD4+ T cells and response to their blockade are dependent on lineage and function

2021 ◽  
Author(s):  
Elsa Brunet-Ratnasingham ◽  
Antigoni Morou ◽  
Mathieu Dube ◽  
Julia Niessl ◽  
Amy E. Baxter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Immune Checkpoints ◽  
Chronic Infections ◽  
Cell Functions ◽  
Art Initiation ◽  
Specific Regulation ◽  
And Function

Background: Antigen-specific T cell impairment is observed in chronic infections. CD4+ T cells are diverse in phenotype and function; how their different lineages are impacted by inhibitory immune checkpoints (IC) is unknown. Methods: We examined IC expression and function in HIV-specific CD4+ T cells of viremic individuals prior to ART initiation and persons with spontaneous or therapy-induced viral suppression. We investigated IC patterns associated with exhaustion-related transcription factors and chemokine receptors using cytokine-independent activation-induced marker assays. We determined effector functions representative of TFH, TH1 and TH17/TH22 using ultra-sensitive RNA flow cytometric fluorescence in situ hybridization (FISH), and their response to IC blockade. Findings: The dysfunction-related transcription factor TOX was elevated in HIV-specific CD4+ T cells of viremic patients, and its expression was associated with lineage differentiation. We observed a hierarchy of PD-1, TIGIT and CD200 expression associated with both infection status and effector profile. In vitro responsiveness to PD-L1 blockade varied with defined CD4+ T cell functions rather than IC expression levels: frequencies of cells with TH1- and TH17/TH22-, but not TFH-related functions, increased. Response to PD-L1 blockade was strongest in viremic participants and reduced after ART initiation. Interpretation: Our data highlight a polarization-specific regulation of IC expression and differing sensitivities of antigen-specific Thelper subsets to PD-1-mediated inhibition. This heterogeneity may direct ICB efficacy on CD4+ T cells in HIV infection.

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