Lymphocyte proliferative responses to human immunodeficiency virus antigens in vitro.

Krowka, John F.; Stites, Daniel P.; Jain, S. N; Steimer, Kathelyn S.; George-Nascimento, Carlos; Gyenes, A; Barr, Philip J.; Hollander, Harry; Moss, Andrew R.; Homsy, Jacques

doi:10.1172/jci114001

Cited by 73 publications

(41 citation statements)

References 30 publications

(28 reference statements)

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“…In contrast to findings for HAART-treated individuals, strong HIV-1-specific lymphoproliferative responses in untreated HIV-1-infected subjects with chronic progressive disease have rarely been observed (5,20,37,39). There are two major alternative explanations that could account for the loss or absence of measurable HIV-1-specific proliferative re- sponses in the clinical setting of active viral replication.…”

Section: Discussionmentioning

confidence: 86%

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4⁺T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

Palmer

Boritz

Blyveis

et al. 2002

J Virol

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One hallmark of uncontrolled, chronic human immunodeficiency virus type 1 (HIV-1) infection is the absence of strong HIV-1-specific, CD4؉ T-cell-proliferative responses, yet the mechanism underlying this T helper (Th)-cell defect remains controversial. To better understand the impact of HIV-1 replication on Th-cell function, we compared the frequency of CD4 ؉ Th-cell responses based on production of gamma interferon to lymphoproliferative responses directed against HIV-1 proteins in HIV-1-infected subjects with active in vivo viral replication versus those on suppressed highly active antiretroviral therapy (HAART). No statistically significant differences in the frequencies of cytokine-secreting, HIV-1-specific CD4؉ T cells between the donor groups were found, despite differences in viral load and treatment status. However, HIV-1-specific lymphoproliferative responses were significantly greater in the subjects with HAART suppression than in subjects with active viral replication. Similar levels of HIV-1 RNA were measured in T-cell cultures stimulated with HIV-1 antigens regardless of donor in vivo viral loads, but only HIV-1-specific CD4 ؉ T cells from subjects with HAART suppression proliferated in vitro, suggesting that HIV-1 replication in vitro does not preclude HIV-1-specific lymphoproliferation. This study demonstrates a discordance between the frequency and proliferative capacity of HIV-1-specific CD4 ؉ T cells in subjects with ongoing in vivo viral replication and suggests that in vivo HIV-1 replication contributes to the observed defect in HIV-1-specific CD4 ؉ T-cell proliferation.

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Section: Discussionmentioning

confidence: 86%

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4⁺T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

Palmer

Boritz

Blyveis

et al. 2002

J Virol

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“…This is in line with data reported by Pinto et al ., who studied T helper cell reactivities to SIV synthetic peptides and HIV-2 recombinant antigens [45,46]. In contrast, in early studies of HIV-1-infected patients, virus-specific lymphocyte-proliferative responses were usually weak [57,58]. However, in a more recent study strong HIV-1-specific lymphocyte-proliferative responses were demonstrated in selected cases of LTNP and in individuals with primary HIV-1 infection who had received early antiretroviral therapy [10].…”

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau

Andersson

Larsen

Silva

et al. 2005

Clinical and Experimental Immunology

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SummaryHuman immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes > > > > 2, compared to one out of 49 of the HIV-negative controls ( P = = = = 0·003 and P < < < < 0·0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.

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“…In addition, the helper T cell responses generated by a soluble antigen may, on virus infection, play an important role complementing the antibodies present. Healthy HIV-seropositive individuals have been known to be depleted of helper CD4+ T cells capable of recognizing virus-specific antigens, including gp120 [39,40]. In contrast, some seronegative individuals with HIV-infected partners have detectable levels of HIV-specific helper T cells [41]indicating a possible role for this lymphocyte subset in protective immunity.…”

Section: Discussionmentioning

confidence: 99%

Safety and Immunogenicity of a Genetically Engineered Human Immunodeficiency Virus Vaccine

Wintsch

Chaignat

Braun

et al. 1991

Journal of Infectious Diseases

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Lymphocyte proliferative responses to human immunodeficiency virus antigens in vitro.

Cited by 73 publications

References 30 publications

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4⁺T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4⁺T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau

Safety and Immunogenicity of a Genetically Engineered Human Immunodeficiency Virus Vaccine

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Lymphocyte proliferative responses to human immunodeficiency virus antigens in vitro.

Cited by 73 publications

References 30 publications

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4+T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4+T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau

Safety and Immunogenicity of a Genetically Engineered Human Immunodeficiency Virus Vaccine

Contact Info

Product

Resources

About

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4⁺T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4⁺T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication