CD4+ T-Lymphocyte Nadir and the Effect of Highly Active Antiretroviral Therapy on Phenotypic and Functional Immune Restoration in HIV-1 Infection

Lange, Christoph; Valdez, Hernán; Medvik, Kathy; Asaad, Robert; Lederman, Michael M.

doi:10.1006/clim.2001.5164

Cited by 90 publications

(58 citation statements)

References 36 publications

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“…ϩ T-cell proliferative responses to HIV have been observed in patients with control of viral replication, including long-term nonprogressors (LTNP), patients treated with antiretroviral therapy during primary HIV infection, and a proportion of patients with chronic HIV infection on effective therapy (2,5,6,24,29,31,34,35,37,42,43).…”

Section: Most Viral Infections Of Humans Results In the Induction Of Lmentioning

confidence: 99%

Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4⁺T Cells Are a Consequence of Antigen Load

Tilton

Luskin

Johnson

et al. 2007

J Virol

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Section: Most Viral Infections Of Humans Results In the Induction Of Lmentioning

confidence: 99%

Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4⁺T Cells Are a Consequence of Antigen Load

Tilton

Luskin

Johnson

et al. 2007

J Virol

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“…Although proliferative responses are typically absent in untreated patients, there are several recent reports that the prevalence of significant proliferative responses to HIV antigens is as high as 30 to 69% of those receiving effective antiretroviral therapy (1,4,5,11,27,31,39). In addition, a number of recent reports have documented the persistence of HIV-specific CD4 ϩ T cells in the majority of patients by intracellular cytokine staining following stimulation with HIV antigens in crosssectional cohorts (3,34,39,41,54).…”

mentioning

confidence: 99%

Diminished Proliferation of Human Immunodeficiency Virus-Specific CD4⁺T Cells Is Associated with Diminished Interleukin-2 (IL-2) Production and Is Recovered by Exogenous IL-2

Iyasere

Tilton

Johnson

et al. 2003

J Virol

171

124

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Virus-specific CD4؉ T-cell function is thought to play a central role in induction and maintenance of effective CD8؉ T-cell responses in experimental animals or humans. However, the reasons that diminished proliferation of human immunodeficiency virus (HIV)-specific CD4 ؉ T cells is observed in the majority of infected patients and the role of these diminished responses in the loss of control of replication during the chronic phase of HIV infection remain incompletely understood. In a cohort of 15 patients that were selected for particularly strong HIV-specific CD4 ؉ T-cell responses, the effects of viremia on these responses were explored. Restriction of HIV replication was not observed during one to eight interruptions of antiretroviral therapy in the majority of patients (12 of 15). In each case, proliferative responses to HIV antigens were rapidly inhibited during viremia. The frequencies of cells that produce IFN-␥ in response to Gag, Pol, and Nef peptide pools were maintained during an interruption of therapy. In a subset of patients with elevated frequencies of interleukin-2 (IL-2)-producing cells, IL-2 production in response to HIV antigens was diminished during viremia. Addition of exogenous IL-2 was sufficient to rescue in vitro proliferation of DR0101 class II Gag or Pol tetramer؉ or total-Gag-specific CD4 ؉ T cells. These observations suggest that, during viremia, diminished in vitro proliferation of HIV-specific CD4 ؉ T cells is likely related to diminished IL-2 production. These results also suggest that relatively high frequencies of HIV-specific CD4 ؉ T cells persist in the peripheral blood during viremia, are not replicatively senescent, and proliferate when IL-2 is provided exogenously.

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“…Effect of CD4 cell nadir and duration of viral load suppression on LPS-induced proliferative augmentation. There are numerous studies that have evaluated the effect of CD4 T-cell nadir (6,25,40) and the duration of undetectable viral load as determinants of cellular immune recovery after HAART (33,37,40). The data have been varied, with some studies able to show a response after viral load suppression (1, 2, 35, 37) and others not able to do so (4,13,34,40).…”

Section: Vol 10 2003 Enhanced Pbl Proliferation To Antigen 759mentioning

confidence: 99%

Antigen-Presenting Cell Modulation Induces a Memory Response to p24 in Peripheral Blood Leukocytes from Human Immunodeficiency Virus-Infected Individuals

Kolber

Saenz

2003

Clin Vaccine Immunol

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The accurate determination of human immunodeficiency virus type 1 (HIV-1)-specific proliferative responses is critically important when evaluating immune recovery after highly active antiretroviral therapy. Using a new assay to enhance proliferative responses to recall and HIV antigen, we addressed the questions of whether viral load affects cellular immunity and whether long-term viral load suppression results in loss of antigen-specific responder cells. This assay is based on the fact that lipopolysaccharide (LPS) can augment proliferative responses to antigen after monocyte adherence to a tissue culture plate. Twenty-six HIV-1-infected individuals donated peripheral blood leukocytes (PBL). Proliferation assays against p24, using LPS and cell adherence, were performed on all samples. Medical record abstraction provided information on CD4 cell nadir and time of viral load suppression. PBL from HIV-1-infected individuals with a viral load of <200 copies/ml had a significant proliferative response and a stimulation index of >5 to p24 (12 of 15) compared to those with a viral burden (2 of 11), using the LPS-adherence assay. Proliferative responses to p24 could be found in PBL from virally suppressed donors independent of the CD4 cell nadirs and in the majority of the donors who were virally suppressed for >10 months (7 of 10). The data presented here demonstrate that LPS and monocyte adherence provide a sensitive and specific way to boost proliferative responses to recall and HIV antigens.The impact of highly active antiretroviral therapy (HAART) on immune reconstitution has been clearly demonstrated in those individuals with advanced disease. When a human immunodeficiency virus type 1 (HIV-1)-infected individual with AIDS is aggressively treated with antiretroviral therapy, the viral load is suppressed and the CD4 count frequently is elevated above 200 cells/mm 3 . This permits discontinuation of prophylaxis for opportunistic infections and, in the long term, results in an enhanced period of survival and a decrease in disease progression. However, there are still numerous questions regarding the level of cellular immunity and which factors affect this parameter.Although it is known that defects in the immune repertoire exist early in infection (31, 36) and progress as the disease advances (12), the ability to reconstitute immunity most likely depends on numerous host factors and comorbid conditions. As a further confounding variable, the role of the viral load as an independent predictor of disease progression for CD4 counts greater than 350 cells/mm 3 has been difficult to ascertain (22), even in light of the in vitro data suggesting immunesuppressive effects of the virus on proliferation to recall and HIV-1 antigens (28,30,37). Incomplete reconstitution in some individuals is suggested by the fact that the incidence of malignancy continues to be high in individuals infected with and treated for their HIV-1 disease (9,27).With the ongoing efforts in HIV vaccine research, the ability to identify individuals with ...

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CD4+ T-Lymphocyte Nadir and the Effect of Highly Active Antiretroviral Therapy on Phenotypic and Functional Immune Restoration in HIV-1 Infection

Cited by 90 publications

References 36 publications

Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4⁺T Cells Are a Consequence of Antigen Load

Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4⁺T Cells Are a Consequence of Antigen Load

Diminished Proliferation of Human Immunodeficiency Virus-Specific CD4⁺T Cells Is Associated with Diminished Interleukin-2 (IL-2) Production and Is Recovered by Exogenous IL-2

Antigen-Presenting Cell Modulation Induces a Memory Response to p24 in Peripheral Blood Leukocytes from Human Immunodeficiency Virus-Infected Individuals

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CD4+ T-Lymphocyte Nadir and the Effect of Highly Active Antiretroviral Therapy on Phenotypic and Functional Immune Restoration in HIV-1 Infection

Cited by 90 publications

References 36 publications

Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4+T Cells Are a Consequence of Antigen Load

Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4+T Cells Are a Consequence of Antigen Load

Diminished Proliferation of Human Immunodeficiency Virus-Specific CD4+T Cells Is Associated with Diminished Interleukin-2 (IL-2) Production and Is Recovered by Exogenous IL-2

Antigen-Presenting Cell Modulation Induces a Memory Response to p24 in Peripheral Blood Leukocytes from Human Immunodeficiency Virus-Infected Individuals

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Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4⁺T Cells Are a Consequence of Antigen Load

Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4⁺T Cells Are a Consequence of Antigen Load

Diminished Proliferation of Human Immunodeficiency Virus-Specific CD4⁺T Cells Is Associated with Diminished Interleukin-2 (IL-2) Production and Is Recovered by Exogenous IL-2