T Regulatory Cell Induced Foxp3 Binds theIL2, IFNγ, andTNFα Promoters in Virus-Specific CD8+T Cells from Feline Immunodeficiency Virus Infected Cats

ABSTRACT Perforin-mediated cytotoxicity is a major effector function of virus-specific CD8 T cells. We have investigated the expression of perforin in the gut, an important site of simian immunodeficiency virus (SIV) pathogenesis, during experimental SIV infection of rhesus macaques. We observed significant increases in perforin protein and mRNA expression levels in the colons of SIV-infected macaques as early as 21 days after infection. However, during chronic infection, despite ongoing viral replication, perforin expression returned to levels similar to those detected in SIV-naïve animals. These findings demonstrate the presence of a robust perforin-positive response in gastrointestinal CD8 T cells during acute, but not chronic, SIV infection.

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4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression

PLoS ONE ◽

10.1371/journal.pone.0153088 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0153088 ◽

Cited By ~ 12

Author(s):

Hampartsoum B. Barsoumian ◽

Esma S. Yolcu ◽

Haval Shirwan

Keyword(s):

T Cells ◽

T Regulatory Cell ◽

Regulatory Cell ◽

Cell Suppression

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Selective anergy of V beta 8+ T cells in human immunodeficiency virus-infected individuals.

Journal of Experimental Medicine ◽

10.1084/jem.179.2.413 ◽

1994 ◽

Vol 179 (2) ◽

pp. 413-424 ◽

Cited By ~ 33

Author(s):

G Dadaglio ◽

S Garcia ◽

L Montagnier ◽

M L Gougeon

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

T Cell ◽

Hiv Infection ◽

Cd8 T Cells ◽

Clinical Status ◽

Interleukin 2 ◽

Cell Subset ◽

T Cell Subset ◽

Immunodeficiency Virus

We have analyzed the V beta usage by CD4+ and CD8+ T cells from human immunodeficiency virus (HIV)-infected individuals in response to an in vitro stimulation with the superantigenic erythrogenic toxin A (ETA) of Streptococcus pyogenes. ETA amplifies specifically CD4+ and CD8+ T cells from control donors expressing the V beta 8 and the V beta 12 elements. When peripheral T cells from asymptomatic HIV-infected individuals were stimulated with ETA, there was a complete lack of activation of the V beta 8+ T cell subset, whereas the V beta 12+ T cell subset responded normally to the superantigen. This V beta-specific anergy, which was also observed in response to staphylococcal enterotoxin E (SEE), affected both CD4+ and CD8+ T cells and represented an intrinsic functional defect rather than a specific lack of response to bacterial superantigens since it was also observed after a stimulation with V beta 8 monoclonal antibodies. The V beta 8 anergic T cells did not express interleukin 2 receptors (IL-2Rs) and failed to proliferate in response to exogenous IL-2 or IL-4, suggesting that this anergy was not a reversible process, at least by the use of these cytokines. The unresponsiveness of the V beta 8 T cell subset is frequent since it was found in 56% of the patients studied, and comparison of the clinical status of responder vs. anergic patients indicated that the only known common factor between them was HIV infection. In addition, it is noteworthy that the anergy of the V beta 8 subset may be a very early phenomenon since it was found in a patient at Centers for Disease Control stage I of the disease. These data provide evidence that a dominant superantigen may be involved in the course of HIV infection and that the contribution of HIV has to be considered.

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Effect of infection with mixed Eimeria species on T cells and T regulatory cell properties

The Journal of Applied Poultry Research ◽

10.3382/japr/pfw026 ◽

2016 ◽

Vol 25 (3) ◽

pp. 407-413 ◽

Cited By ~ 2

Author(s):

M.W.S. Walston ◽

R. Shanmugasundaram ◽

R.K. Selvaraj

Keyword(s):

T Cells ◽

Eimeria Species ◽

T Regulatory Cell ◽

Regulatory Cell

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Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection

Blood ◽

10.1182/blood.v96.9.3094 ◽

2000 ◽

Vol 96 (9) ◽

pp. 3094-3101 ◽

Cited By ~ 201

Author(s):

Premlata Shankar ◽

Melissa Russo ◽

Brooke Harnisch ◽

Mark Patterson ◽

Paul Skolnik ◽

...

Keyword(s):

T Cells ◽

Reverse Transcriptase ◽

Cd8 T Cells ◽

Culture Medium ◽

Significant Proportion ◽

Histocompatibility Complex ◽

Immunodeficiency Virus ◽

Ifn Γ ◽

Mixed Pattern

Abstract The functional status of circulating human immunodeficiency (HIV)-specific CD8 T cells in chronically infected subjects was evaluated. By flow cytometry, only 5 of 7 subjects had detectable CD8 T cells that produced IFN-γ after stimulation with HIV-infected primary CD4 T cells. In 2 subjects, the frequency of IFN-γ–producing cells increased 4-fold when IL-2 was added to the culture medium; in another subject, IFN-γ–producing cells could be detected only after IL-2 was added. IFN-γ–producing cells ranged from 0.4% to 3% of CD8 T cells. Major histocompatibility complex–peptide tetramer staining, which identifies antigen-specific T cells irrespective of function, was used to evaluate the proportion of HIV-specific CD8 T cells that may be nonfunctional in vivo. CD8 T cells binding to tetramers complexed to HIV gag epitope SLYNTVATL and reverse transcriptase epitope YTAFTIPSI were identified in 9 of 15 and 5 of 12 HLA-A2–expressing seropositive subjects at frequencies of 0.1% to 1.1% and 0.1 to 0.7%, respectively. Freshly isolated tetramer-positive cells expressed a mixed pattern of memory and effector markers. On average, IFN-γ was produced by less than 25% of tetramer-positive CD8 T cells after stimulation with the relevant gag or reverse transcriptase peptide. In all subjects tested, freshly isolated CD8 T cells were not cytolytic against peptide-pulsed B lymphoblastoid cell line or primary HIV-infected CD4 T-cell targets. Exposure to IL-2 enhanced the cytotoxicity of CD8 T cells against primary HIV-infected CD4 targets in 2 of 2 subjects tested. These results suggest that a significant proportion of HIV-specific CD8 T cells may be functionally compromised in vivo and that some function can be restored by exposure to IL-2.

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Decreased CXCR3+ CD8 T Cells in Advanced Human Immunodeficiency Virus Infection Suggest that a Homing Defect Contributes to Cytotoxic T-Lymphocyte Dysfunction

Journal of Virology ◽

10.1128/jvi.00199-07 ◽

2007 ◽

Vol 81 (16) ◽

pp. 8439-8450 ◽

Cited By ~ 22

Author(s):

Diana M. Brainard ◽

Andrew M. Tager ◽

Joseph Misdraji ◽

Nicole Frahm ◽

Mathias Lichterfeld ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Hiv Infection ◽

Cd8 T Cells ◽

Lymphoid Tissue ◽

Chronic Infection ◽

Advanced Disease ◽

Receptor Expression ◽

Effector Memory ◽

Immunodeficiency Virus

ABSTRACT To exert their cytotoxic function, cytotoxic T-lymphocytes (CTL) must be recruited into infected lymphoid tissue where the majority of human immunodeficiency virus (HIV) replication occurs. Normally, effector T cells exit lymph nodes (LNs) and home to peripheral sites of infection. How HIV-specific CTL migrate into lymphoid tissue from which they are normally excluded is unknown. We investigated which chemokines and receptors mediate this reverse homing and whether impairment of this homing could contribute to CTL dysfunction as HIV infection progresses. Analysis of CTL chemokine receptor expression in the blood and LNs of untreated HIV-infected individuals with stable, chronic infection or advanced disease demonstrated that LNs were enriched for CXCR3+ CD8 T cells in all subjects, suggesting a key role for this receptor in CTL homing to infected lymphoid tissue. Compared to subjects with chronic infection, however, subjects with advanced disease had fewer CXCR3+ CD8 T cells in blood and LNs. CXCR3 expression on bulk and HIV-specific CD8 T cells correlated positively with CD4 count and negatively with viral load. In advanced infection, there was an accumulation of HIV-specific CD8 T cells at the effector memory stage; however, decreased numbers of CXCR3+ CD8 T cells were seen across all maturation subsets. Plasma CXCL9 and CXCL10 were elevated in both infected groups in comparison to the levels in uninfected controls, whereas lower mRNA levels of CXCR3 ligands and CD8 in LNs were seen in advanced infection. These data suggest that both CXCR3+ CD8 T cells and LN CXCR3 ligands decrease as HIV infection progresses, resulting in reduced homing of CTL into LNs and contributing to immune dysfunction.

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Persistent Recognition of Autologous Virus by High-Avidity CD8 T Cells in Chronic, Progressive Human Immunodeficiency Virus Type 1 Infection

Journal of Virology ◽

10.1128/jvi.78.2.630-641.2004 ◽

2004 ◽

Vol 78 (2) ◽

pp. 630-641 ◽

Cited By ~ 108

Author(s):

R. Draenert ◽

C. L. Verrill ◽

Y. Tang ◽

T. M. Allen ◽

A. G. Wurcel ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

T Cell Responses ◽

Cd8 T Cell ◽

Gamma Interferon ◽

High Avidity ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Stage Infection

ABSTRACT CD8 T-cell responses are thought to be crucial for control of viremia in human immunodeficiency virus (HIV) infection but ultimately fail to control viremia in most infected persons. Studies in acute infection have demonstrated strong CD8-mediated selection pressure and evolution of mutations conferring escape from recognition, but the ability of CD8 T-cell responses that persist in late-stage infection to recognize viruses present in vivo has not been determined. Therefore, we studied 24 subjects with advanced HIV disease (median viral load = 142,000 copies/ml; median CD4 count = 71/μl) and determined HIV-1-specific CD8 T-cell responses to all expressed viral proteins using overlapping peptides by gamma interferon Elispot assay. Chronic-stage virus was sequenced to evaluate autologous sequences within Gag epitopes, and functional avidity of detected responses was determined. In these subjects, the median number of epitopic regions targeted was 13 (range, 2 to 39) and the median cumulative magnitude of CD8 T-cell responses was 5,760 spot-forming cells/106 peripheral blood mononuclear cells (range, 185 to 24,700). On average six (range, one to 8) proteins were targeted. For 89% of evaluated CD8 T-cell responses, the autologous viral sequence was predicted to be well recognized by these responses and the majority of analyzed optimal epitopes were recognized with medium to high functional avidity by the contemporary CD8 T cells. Withdrawal of antigen by highly active antiretroviral therapy led to a significant decline both in breadth (P = 0.032) and magnitude (P = 0.0098) of these CD8 T-cell responses, providing further evidence that these responses had been driven by recognition of autologous virus. These results indicate that strong, broadly directed, and high-avidity gamma-interferon-positive CD8 T-cells directed at autologous virus persist in late disease stages, and the absence of mutations within viral epitopes indicates a lack of strong selection pressure mediated by these responses. These data imply functional impairment of CD8 T-cell responses in late-stage infection that may not be reflected by gamma interferon-based screening techniques.

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