An early defect in primary and secondary T cell responses in asymptomatic cats during acute feline immunodeficiency virus (FIV) infection

Abstract AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in human immunodeficiency virus (HIV) controllers start antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Before ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. During ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.

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Comprehensive Epitope Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses Directed against the Entire Expressed HIV-1 Genome Demonstrate Broadly Directed Responses, but No Correlation to Viral Load

Journal of Virology ◽

10.1128/jvi.77.3.2081-2092.2003 ◽

2003 ◽

Vol 77 (3) ◽

pp. 2081-2092 ◽

Cited By ~ 513

Author(s):

M. M. Addo ◽

X. G. Yu ◽

A. Rathod ◽

D. Cohen ◽

R. L. Eldridge ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Protein Subunits ◽

Cell Responses ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Total Magnitude ◽

Cellular Immune ◽

Hiv 1

ABSTRACT Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/106 PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

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Increased Loss of CCR5+ CD45RA− CD4+ T Cells in CD8+ Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Journal of Virology ◽

10.1128/jvi.02748-07 ◽

2008 ◽

Vol 82 (11) ◽

pp. 5618-5630 ◽

Cited By ~ 23

Author(s):

Ronald S. Veazey ◽

Paula M. Acierno ◽

Kimberly J. McEvers ◽

Susanne H. C. Baumeister ◽

Gabriel J. Foster ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lymph Nodes ◽

Simian Immunodeficiency Virus ◽

Peripheral Blood ◽

T Cell Responses ◽

Lymphocyte Depletion ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Siv Infection

ABSTRACT Previously we have shown that CD8+ T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4+ T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8+ T-cell responses on the magnitude of the CD4+ T-cell depletion, we investigated the effect of CD8+ lymphocyte depletion during primary SIV infection on CD4+ T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8+ lymphocyte-depletion changed the dynamics of CD4+ T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4+ T cells were restored to baseline levels. These CD4+ T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8+ lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5+ CD45RA− CD4+ T cells in CD8+ lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4+ T cells were eliminated more efficiently in CD8+ lymphocyte-depleted animals. Also, CD8+ lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4+ T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8+ T-cell responses are absolutely critical to initiate at least partial control of SIV infection.

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T Cell Responses During Human Immunodeficiency Virus (HIV)-1 Infection

Control of Innate and Adaptive Immune Responses during Infectious Diseases ◽

10.1007/978-1-4614-0484-2_8 ◽

2011 ◽

pp. 141-169

Author(s):

Claire A. Chougnet ◽

Barbara L. Shacklett

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

T Cell Responses ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

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CD4+ T Cell Responses to Simian Immunodeficiency Virus

Current Topics in Microbiology and Immunology - Simian Immunodeficiency Virus ◽

10.1007/978-3-642-78536-8_9 ◽

1994 ◽

pp. 161-173

Author(s):

K. H. G. Mills ◽

W. C. Jones

Keyword(s):

T Cell ◽

Simian Immunodeficiency Virus ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses ◽

Immunodeficiency Virus

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Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy668 ◽

2019 ◽

Vol 219 (9) ◽

pp. 1407-1417 ◽

Cited By ~ 1

Author(s):

Maximilian Muenchhoff ◽

Emily Adland ◽

Julia Roider ◽

Henrik Kløverpris ◽

Alasdair Leslie ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Antiretroviral Therapy ◽

Immune Reconstitution ◽

T Cell Responses ◽

Cell Phenotype ◽

Memory Phenotype ◽

Cell Responses ◽

Immune Exhaustion ◽

Immunodeficiency Virus

Abstract Background Susceptibility to coinfections in human immunodeficiency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell responses in children before and after ART. Methods We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)-specific T-cell responses before and 1 year after initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays after in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation. Results We observed differential, pathogen-specific changes after 1 year of ART in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased programmed cell death 1 (PD-1) expression. The proliferative capacity of HIV- and PPD-specific responses increased after 1 year of ART. Of note, the recovery of CMV- and TB-specific responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively). Conclusions Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. The PD-1 pathway represents a potential target for immunotherapy in HIV-infected patients on ART with insufficient immune reconstitution.

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Association between Virus-Specific T-Cell Responses and Plasma Viral Load in Human Immunodeficiency Virus Type 1 Subtype C Infection

Journal of Virology ◽

10.1128/jvi.77.2.882-890.2003 ◽

2003 ◽

Vol 77 (2) ◽

pp. 882-890 ◽

Cited By ~ 116

Author(s):

V. Novitsky ◽

P. Gilbert ◽

T. Peter ◽

M. F. McLane ◽

S. Gaolekwe ◽

...

Keyword(s):

Viral Load ◽

T Cell ◽

Immune Responses ◽

Plasma Viral Load ◽

T Cell Responses ◽

Subtype C ◽

Cell Responses ◽

Immunodeficiency Virus ◽

T Cell Immune Responses

ABSTRACT Virus-specific T-cell immune responses are important in restraint of human immunodeficiency virus type 1 (HIV-1) replication and control of disease. Plasma viral load is a key determinant of disease progression and infectiousness in HIV infection. Although HIV-1 subtype C (HIV-1C) is the predominant virus in the AIDS epidemic worldwide, the relationship between HIV-1C-specific T-cell immune responses and plasma viral load has not been elucidated. In the present study we address (i) the association between the level of plasma viral load and virus-specific immune responses to different HIV-1C proteins and their subregions and (ii) the specifics of correlation between plasma viral load and T-cell responses within the major histocompatibility complex (MHC) class I HLA supertypes. Virus-specific immune responses in the natural course of HIV-1C infection were analyzed in the gamma interferon (IFN-γ)-enzyme-linked immunospot assay by using synthetic overlapping peptides corresponding to the HIV-1C consensus sequence. For Gag p24, a correlation was seen between better T-cell responses and lower plasma viral load. For Nef, an opposite trend was observed where a higher T-cell response was more likely to be associated with a higher viral load. At the level of the HLA supertypes, a lower viral load was associated with higher T-cell responses to Gag p24 within the HLA A2, A24, B27, and B58 supertypes, in contrast to the absence of such a correlation within the HLA B44 supertype. The present study demonstrated differential correlations (or trends to correlation) in various HIV-1C proteins, suggesting (i) an important role of the HIV-1C Gag p24-specific immune responses in control of viremia and (ii) more rapid viral escape from immune responses to Nef with no restraint of plasma viral load. Correlations between the level of IFN-γ-secreting T cells and viral load within the MHC class I HLA supertypes should be considered in HIV vaccine design and efficacy trials.

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