Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

Background & aims HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays. Results We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA’s therapies.

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CD4 T cell control primary measles virus infection of the CNS: Regulation is dependent on combined activity with either CD8 T cells or with B cells: CD4, CD8 or B cells alone are ineffective

Virology ◽

10.1016/j.virol.2006.01.050 ◽

2006 ◽

Vol 347 (1) ◽

pp. 234-245 ◽

Cited By ~ 33

Author(s):

Antoinette Tishon ◽

Hanna Lewicki ◽

Abegail Andaya ◽

Dorian McGavern ◽

Lee Martin ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Virus Infection ◽

Cd8 T Cells ◽

Measles Virus ◽

Cd4 T Cell ◽

Cell Control

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Anti–4-1bb Monoclonal Antibodies Abrogate T Cell–Dependent Humoral Immune Responses in Vivo through the Induction of Helper T Cell Anergy

Journal of Experimental Medicine ◽

10.1084/jem.190.10.1535 ◽

1999 ◽

Vol 190 (10) ◽

pp. 1535-1540 ◽

Cited By ~ 137

Author(s):

Robert S. Mittler ◽

Tina S. Bailey ◽

Kerry Klussman ◽

Mark D. Trailsmith ◽

Michael K. Hoffmann

Keyword(s):

Immune Response ◽

T Cells ◽

Monoclonal Antibodies ◽

T Cell ◽

B Cells ◽

Humoral Immunity ◽

Cd8 T Cells ◽

Immunodeficient Mice ◽

Humoral Immune

The 4-1BB receptor (CDw137), a member of the tumor necrosis factor receptor superfamily, has been shown to costimulate the activation of T cells. Here we show that anti–mouse 4-1BB monoclonal antibodies (mAbs) inhibit thymus-dependent antibody production by B cells. Injection of anti–4-1BB mAbs into mice being immunized with cellular or soluble protein antigens induced long-term anergy of antigen-specific T cells. The immune response to the type II T cell–independent antigen trinintrophenol-conjugated Ficoll, however, was not suppressed. Inhibition of humoral immunity occurred only when anti–4-1BB mAb was given within 1 wk after immunization. Anti–4-1BB inhibition was observed in mice lacking functional CD8+ T cells, indicating that CD8+ T cells were not required for the induction of anergy. Analysis of the requirements for the anti–4-1BB–mediated inhibition of humoral immunity revealed that suppression could not be adoptively transferred with T cells from anti–4-1BB–treated mice. Transfer of BALB/c splenic T cells from sheep red blood cell (SRBC)-immunized and anti–4-1BB–treated mice together with normal BALB/c B cells into C.B-17 severe combined immunodeficient mice failed to generate an anti-SRBC response. However, B cells from the SRBC-immunized, anti–4-1BB–treated BALB/c mice, together with normal naive T cells, exhibited a normal humoral immune response against SRBC after transfer, demonstrating that SRBC-specific B cells were left unaffected by anti–4-1BB mAbs.

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Fas-Mediated Inhibition of CD4+ T Cell Priming Results in Dominance of Type 1 CD8+ T Cells in the Immune Response to the Contact Sensitizer Trinitrophenyl

The Journal of Immunology ◽

10.4049/jimmunol.173.5.3178 ◽

2004 ◽

Vol 173 (5) ◽

pp. 3178-3185 ◽

Cited By ~ 25

Author(s):

Stefan F. Martin ◽

Jan C. Dudda ◽

Virginie Delattre ◽

Eva Bachtanian ◽

Cornelia Leicht ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Cd4 T Cell ◽

T Cell Priming

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CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection

Journal of Experimental Medicine ◽

10.1084/jem.20130904 ◽

2014 ◽

Vol 211 (4) ◽

pp. 623-633 ◽

Cited By ~ 26

Author(s):

Victor S. Cortez ◽

Luisa Cervantes-Barragan ◽

Christina Song ◽

Susan Gilfillan ◽

Keely G. McDonald ◽

...

Keyword(s):

T Cells ◽

Cell Adhesion ◽

Steady State ◽

T Cell ◽

Intestinal Mucosa ◽

Cd8 T Cells ◽

Cd4 T Cells ◽

Cell Adhesion Molecule ◽

Cd4 T Cell ◽

Th1 Response

Retention of lymphocytes in the intestinal mucosa requires specialized chemokine receptors and adhesion molecules. We find that both CD4+CD8+ and CD4+ T cells in the intestinal epithelium, as well as CD8+ T cells in the intestinal mucosa and mesenteric lymph nodes, express the cell adhesion molecule class I–restricted T cell–associated molecule (Crtam) upon activation, whereas the ligand of Crtam, cell adhesion molecule 1 (Cadm1), is expressed on gut CD103+DCs. Lack of Crtam–Cadm1 interactions in Crtam−/− and Cadm1−/− mice results in loss of CD4+CD8+ T cells, which arise from mucosal CD4+ T cells that acquire a CD8 lineage expression profile. After acute oral infection with Toxoplasma gondii, both WT and Crtam−/− mice mounted a robust TH1 response, but markedly fewer TH17 cells were present in the intestinal mucosa of Crtam−/− mice. The almost exclusive TH1 response in Crtam−/− mice resulted in more efficient control of intestinal T. gondii infection. Thus, Crtam–Cadm1 interactions have a major impact on the residency and maintenance of CD4+CD8+ T cells in the gut mucosa in the steady state. During pathogenic infection, Crtam–Cadm1 interactions regulate the dynamic equilibrium between newly formed CD4+ T cells and their retention in the gut, thereby shaping representation of disparate CD4+ T cell subsets and the overall quality of the CD4+ T cell response.

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An Optimized CD4 T-Cell Response Can Control Productive and Latent Gammaherpesvirus Infection

Journal of Virology ◽

10.1128/jvi.78.13.6827-6835.2004 ◽

2004 ◽

Vol 78 (13) ◽

pp. 6827-6835 ◽

Cited By ~ 42

Author(s):

Rebecca L. Sparks-Thissen ◽

Douglas C. Braaten ◽

Scott Kreher ◽

Samuel H. Speck ◽

Herbert W. Virgin

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

B Cell ◽

Cd8 T Cells ◽

Cd4 T Cells ◽

Acute Infection ◽

Cd8 T Cell ◽

T Cell Response ◽

Cd4 T Cell

ABSTRACT CD4 T cells are important for control of infection with murine gammaherpesvirus 68 (γHV68), but it is not known whether CD4 T cells function via provision of help to other lymphocyte subsets, such as B cells and CD8 T cells, or have an independent antiviral function. Moreover, under conditions of natural infection, the CD4 T-cell response is not sufficient to eliminate infection. To determine the functional capacities of CD4 T cells under optimal or near-optimal conditions and to determine whether CD4 T cells can control γHV68 infection in the absence of CD8 T cells or B cells, we studied the effect of ovalbumin (OVA)-specific CD4 T cells on infection with a recombinant γHV68 that expresses OVA. OVA-specific CD4 T cells limited acute γHV68 replication and prolonged the life of infected T-cell receptor-transgenic RAG (DO.11.10/RAG) mice, demonstrating CD4 T-cell antiviral activity, independent of CD8 T cells and B cells. Despite CD4 T-cell-mediated control of acute infection, latent infection was established in DO.11.10/RAG mice. However, OVA-specific CD4 T cells reduced the frequency of latently infected cells both early (16 days postinfection) and late (42 days postinfection) after infection of mice containing CD8 T cells and B cells (DO.11.10 mice). These results show that OVA-specific CD4 T cells have B-cell and CD8 T-cell-independent antiviral functions in the control of acute infection and can, in the absence of preexisting CD8 T-cell or B-cell immunity, inhibit the establishment of gammaherpesvirus latency.

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