HLA-DR-Restricted Peptides Identified in The Nef Protein Can Induce HIV Type 1-Specific IL-2/IFN-γ-Secreting CD4+And CD4+/CD8+T Cells in Humans after Lipopeptide Vaccination

2007 ◽  
Vol 23 (3) ◽  
pp. 427-437 ◽  
Author(s):  
Hanne Gahery ◽  
Suzanne Figueiredo ◽  
Catherine Texier ◽  
Sandra Pouvelle-Moratille ◽  
Lucie Ourth ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hla Dr ◽  
Ifn Γ ◽  
Hiv Type 1

Increased Expression of TLR7 in CD8+T Cells Leads to TLR7-Mediated Activation and Accessory Cell-Dependent IFN-γ Production in HIV Type 1 Infection

2009 ◽  
Vol 25 (12) ◽  
pp. 1287-1295 ◽  
Author(s):  
Yang Song ◽  
Yan Zhuang ◽  
Song Zhai ◽  
Dedong Huang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Accessory Cell ◽  
Ifn Γ ◽  
Hiv Type 1

scholarly journals Clearance of HIV Type 1 Envelope Recombinant Sendai Virus Depends on CD4+T Cells and Interferon-γ But Not B Cells, CD8+T Cells, or Perforin

2010 ◽  
Vol 26 (7) ◽  
pp. 783-793 ◽  
Author(s):  
Sherri L. Surman ◽  
Scott A. Brown ◽  
Bart G. Jones ◽  
David L. Woodland ◽  
Julia L. Hurwitz
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Sendai Virus ◽  
Interferon Γ ◽  
Hiv Type 1

Permissive Conditions for Evolution of PNH Clones Are Characterized by Overproduction of IFN-γ by Clonal CD4 and CD8 T Cells, Fas-L by CTLs, and Promoted by Immunogenetic Background

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4116-4116
Author(s):  
Michael Clemente ◽  
Heather Cazzolli ◽  
Anna Jankowska ◽  
Christine O’Keefe ◽  
Bianca Serio ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Responses ◽  
Strong Trend ◽  
Hla Dr ◽  
Ifn Γ ◽  
Fas L ◽  
Pnh Clone ◽  
Effector Mechanisms

Abstract The association between immune-mediated aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) has been well documented, yet the related immune pathophysiology remains ill-defined. Response of AA patients with PNH clones to immunosuppressive agents such as anti-thymocyte globulin (ATG) and cyclosporine A provides clinical evidence for the involvement of the immune system in the evolution of PNH. The similar immunobiology of PNH and AA is also exemplified by the overrepresentation of HLA-DR*15 in AA, AA/PNH and PNH. To discern the relationship between T cell responses and effector mechanisms we applied a battery of immune tests to patients with these rare diseases. First, using T cell receptor Vβ flow cytometry in a cohort of patients with AA (N=42), AA/PNH (N=15), or PNH (N=18), we identified cytotoxic CD8 T cell (CTL) clonal expansions in 28/42 (66.7%), 9/15 (60%), and 7/18 (38.8%) patients, respectively. CD4 T cell expansions were present in 6/42 of AA (14.3%), 2/15 (13.3%) of AA/PNH, and 2/18 (11.1%) of PNH patients. We then studied whether expanded clones were associated with production of inflammatory cytokines; across the entire cohort, patients with clonal CD8 Vβ expansions demonstrated a significantly increased proportion of IFN-γ producing T cells as well as elevated levels of circulating Fas-L when compared to patients without clonal skewing (p=.032 CD4+IFN-γ+, p=.008 CD8+IFN-γ+, p=.097 sFAS-L). Even more pronounced was the increase in the proportion of IFN-γ producing CD4 T cells in patients with clonal CD4 Vβ expansions (p=.010). Furthermore, while a strong trend toward increased sFAS-L as detected by ELISA was found in patients with CD8 Vβ skewing vs. those without, patients with pronounced CD4 expansions did not produce elevated Fas-L levels, consistent with different effector mechanisms employed by CD4 vs. CD8 T cells. Based on these results we hypothesized that the presence of PNH clones will be associated with activation of immune effector mechanisms. Linear regression analysis of the size of the PNH clone vs. proportion of IFN-γ CTLs displayed a positive correlation that nearly reached statistical significance at α=0.05 (p=.067). A high proportion of CD4 IFN-γ cells (defined by a value above 95% mean confidence intervals of controls) was also associated with the presence of PNH (p=.048). Genetic analysis revealed further clues as to the increased propensity of patients with AA and PNH clones to produce elevated levels of IFN-γ; the hypersecretor genotype T/T for IFN-γ was over-represented in AA (28% vs. 10% in controls, p=.02) and correlated with presence of a PNH clone (35% vs. 14%, p=.01). An essential role of T cells in generating permissive conditions for the evolution of PNH clones is also supported by the immunogenetic relationship of PNH to HLA-DR*15, a relationship which was confirmed in our population of patients: phenotype frequency of HLA DR*15 was 42.8% AA, 40% AA/PNH, 27.8% PNH vs. 17.2% in control group. When HLA DR*15 positive and DR15 negative patients were compared, those with DR*15 displayed a strong trend toward increased proportion of CD8+IFN-γ producing cells (p=.094), previously shown to be elevated in patients with PNH clones. Our results reveal insights into the nature of permissive conditions involving oligoclonal T cell responses, oversecretion of proinflammatory cytokines, and immunogenetic background which together may promote the expansion of PNH clones. Conversely, it remains possible that the cytotoxic milieu may be a result of an immune response directed against intrinsically abnormal PNH clones.

Phagocytosis May Be a Regulatory Mechanism for Myeloid Dendritic Cells to Terminate Type 1 CD8+ T Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1654-1654
Author(s):  
Young-June Kim ◽  
Hal E. Broxmeyer
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Phagocytic Activity ◽  
Regulatory Mechanism ◽  
Gm Csf ◽  
T Cell Immune Responses ◽  
Ifn Γ

Abstract Abstract 1654 Poster Board I-680 CD8+ cytotoxic T cells are often ‘exhausted’ by programmed death-1 (PD-1) signaling, and subsequently the functions of these cells are terminated especially in a tumor environment or upon chronic HIV or HCV infection. Subsets of myeloid cells referred to as myeloid derived suppressor cells (MDSC) or regulatory dendritic cells (DCs) have been implicated in inducing exhaustion or termination of effector CD8+ T cells. To this end, we developed various myeloid-derived dendritic cell (DC) types in vitro from human CD14+ monocytes using M-CSF or GM-CSF in the presence of IL-4 with/without other cytokines, and characterized these DCs with respect to their capacity to induce PD-1 expression on and exhaustion of CD8+ T cells. We then assessed their impact on longevity of CD8+ T cells following coculture. Myeloid DCs developed in vitro with M-CSF and IL-4 for 5 days (referred to as M-DC) did not express ligand for PD-1 (PD-L1) nor did they induce PD-1 on CD8+ T cells. Thus, using M-DCs as starting cells, we sought determinant factors that could modulate M-DCs to express PD-L1 and thereby induce exhaustion of CD8+ T cells. In order to better monitor exhaustion processes, we incubated human peripheral CD8+ T cells for 5 days in the presence of IL-15, an important cytokine for maintaining viability, before coculture. M-DCs showed little impact on exhaustion or longevity of the CD8+ T cells. IL-10 converted M-DC into a distinct myeloid DC subset (referred to as M-DC/IL-10) with an ability to express PD-L1 as well as to induce PD-1 on cocultured CD8+ T cells. M-DC/IL-10 cells markedly suppressed proliferation of cocultured CD8+ T cells. M-DC/IL-10 cells were morphologically unique with many granules and filamentous structures around the cell periphery. These IL-10 effects on M-DC were completely abrogated in the presence of TNF-á. M-DC/IL-10 cells could be further differentiated into another myeloid DC subset in the presence of IFN-γ (referred to as M-DC/IL-10/IFN-γ) with an ability to express even higher levels of PD-L1 compared to M-DC/IL-10 cells. The most remarkable effect of M-DC/IL-10/IFN-γ cells on cocultured CD8+ T cells was a dramatic loss of CD8+ T cells. Light and confocal microscopic observations indicated that loss of CD8+ T cells was due to phagocytosis by M-DC/IL-10/IFN-γ cells. As IFN-γ, a type 1 cytokine which is induced in CD8+ T cells by IL-12 is essential for phagocytosis, we tested whether IL-12 treatment of CD8+ T cells could further enhance phagocytosis induced by M-DC/IL-10/IFN-γ cells. Indeed, IL-12 treatment greatly increased numbers of phagocytosed CD8+ T cells. In contrast, IL-4 treated CD8+ T cells became resistant to phagocytosis, suggesting IFN-γ producing (type1) CD8+ T cells may be primary target cells for the M-DC/IL-10 cells mediated phagocytosis. CD4+ T cells were not as susceptible as CD8+ T cells to phagocytosis. We failed to detect such phagocytic activity induced by prototype DCs generated with GM-CSF and IL-4. Phagocytic activity was not inhibited by various arginase-1 inhibitors suggesting that nitric oxide signaling may not mediate phagocytic activity. Neutralizing antibody to PD-L1 slightly but significantly lowered phagocytic activity suggesting that PD-L1/PD-1 interaction may be partially involved in this process. Myeloid DCs are thought to be immunogenic, actively inducing T cell immune responses. Our results demonstrate that myeloid DCs may play suppressive roles as well through induction of phagocytic activity, especially against IFN-γ producing CD8+ T cells. This may serve as a regulatory mechanism for type 1 CD8+ T cell immune responses in an IL-10 enriched microenvironment. Disclosures No relevant conflicts of interest to declare.

scholarly journals CD38 Expression in CD8+T Cells Predicts Virological Failure in HIV Type 1–Infected Children Receiving Antiretroviral Therapy

2004 ◽  
Vol 38 (3) ◽  
pp. 412-417 ◽  
Author(s):  
Salvador Resino ◽  
Jose M. Bellon ◽  
M. Dolores Gurbindo ◽  
M. Angeles Munoz‐Fernandez
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
Virological Failure ◽  
Cd38 Expression ◽  
Hiv Type 1

scholarly journals Comparison of Transcriptional Profiles Between CD4+ and CD8+ T Cells in HIV Type 1-Infected Patients

2014 ◽  
Vol 30 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Chaoyu Xu ◽  
Baochun Ye ◽  
Zongping Han ◽  
Mingxing Huang ◽  
Yujia Zhu
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Transcriptional Profiles ◽  
Hiv Type 1

In Vivo Expansion Coincident with Excessive in Vitro Cell Death within the Memory Subset of CD8+ T Cells in HIV Type 1 Infection

1999 ◽  
Vol 15 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Emiliano N. Mugnaini ◽  
Lise L. Haaheim ◽  
Mette Sannes ◽  
Jan E. Brinchmann
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Cd8 T Cells ◽  
Hiv Type 1 ◽  
Memory Subset

scholarly journals Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients from India

2016 ◽  
Vol 90 (24) ◽  
pp. 11259-11278 ◽  
Author(s):  
Anmol Chandele ◽  
Jaturong Sewatanon ◽  
Sivaram Gunisetty ◽  
Mohit Singla ◽  
Nattawat Onlamoon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dengue Virus ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Tcr Signaling ◽  
Hla Dr ◽  
Ifn Γ

ABSTRACT Epidemiological studies suggest that India has the largest number of dengue virus infection cases worldwide. However, there is minimal information about the immunological responses in these patients. CD8 T cells are important in dengue, because they have been implicated in both protection and immunopathology. Here, we provide a detailed analysis of HLA-DR + CD38 + and HLA-DR − CD38 + effector CD8 T cell subsets in dengue patients from India and Thailand. Both CD8 T cell subsets expanded and expressed markers indicative of antigen-driven proliferation, tissue homing, and cytotoxic effector functions, with the HLA-DR + CD38 + subset being the most striking in these effector qualities. The breadth of the dengue-specific CD8 T cell response was diverse, with NS3-specific cells being the most dominant. Interestingly, only a small fraction of these activated effector CD8 T cells produced gamma interferon (IFN-γ) when stimulated with dengue virus peptide pools. Transcriptomics revealed downregulation of key molecules involved in T cell receptor (TCR) signaling. Consistent with this, the majority of these CD8 T cells remained IFN-γ unresponsive even after TCR-dependent polyclonal stimulation (anti-CD3 plus anti-CD28) but produced IFN-γ by TCR-independent polyclonal stimulation (phorbol 12-myristate 13-acetate [PMA] plus ionomycin). Thus, the vast majority of these proliferating, highly differentiated effector CD8 T cells probably acquire TCR refractoriness at the time the patient is experiencing febrile illness that leads to IFN-γ unresponsiveness. Our studies open novel avenues for understanding the mechanisms that fine-tune the balance between CD8 T cell-mediated protective versus pathological effects in dengue. IMPORTANCE Dengue is becoming a global public health concern. Although CD8 T cells have been implicated both in protection and in the cytokine-mediated immunopathology of dengue, how the balance is maintained between these opposing functions remains unknown. We comprehensively characterized CD8 T cell subsets in dengue patients from India and Thailand and show that these cells expand massively and express phenotypes indicative of overwhelming antigenic stimulus and tissue homing/cytotoxic-effector functions but that a vast majority of them fail to produce IFN-γ in vitro . Interestingly, the cells were fully capable of producing the cytokine when stimulated in a T cell receptor (TCR)-independent manner but failed to do so in TCR-dependent stimulation. These results, together with transcriptomics, revealed that the vast majority of these CD8 T cells from dengue patients become cytokine unresponsive due to TCR signaling insufficiencies. These observations open novel avenues for understanding the mechanisms that fine-tune the balance between CD8-mediated protective versus pathological effects.

Cross-Clade Conservation of HIV Type 1 Nef Immunodominant Regions Recognized by CD8+T Cells of HIV Type 1 CRF02_AG-Infected Ivorian (West Africa)

2005 ◽  
Vol 21 (7) ◽  
pp. 620-628 ◽  
Author(s):  
André Inwoley ◽  
Patricia Recordon-Pinson ◽  
Marion Dupuis ◽  
Jessintha Gaston ◽  
Mathieu Genête ◽  
...  
Keyword(s):  
T Cells ◽  
West Africa ◽  
Cd8 T Cells ◽  
Hiv Type 1
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