Severe CD4+ T-Cell Depletion in Gut Lymphoid Tissue during Primary Human Immunodeficiency Virus Type 1 Infection and Substantial Delay in Restoration following Highly Active Antiretroviral Therapy

Moraima Guadalupe, Elizabeth Reay, Sumathi Sankaran-Walters, Thomas P Prindiville, Jason Flamm, Andrew McNeil, Satya Dandekar

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Abstract

Gut-associated lymphoid tissue (GALT) harbors the majority of T lymphocytes in the body and is an important target for human immunodeficiency virus type 1 (HIV-1). We analyzed longitudinal jejunal biopsy samples from HIV-1-infected patients, during both primary and chronic stages of HIV-1 infection, prior to and following the initiation of highly active antiretroviral therapy (HAART) to determine the onset of CD4+ T-cell depletion and the effect of HAART on the restoration of CD4+ T cells in GALT. Severe depletion of intestinal CD4+ T cells occurred during primary HIV-1 infection. Our results showed that the restoration of intestinal CD4+ T cells following HAART in chronically HIV-1-infected patients was substantially delayed and incomplete. In contrast, initiation of HAART during early stages of infection resulted in near-complete restoration of intestinal CD4+ T cells, despite the delay in comparison to peripheral blood CD4+ T-cell recovery. DNA microarray analysis of gene expression profiles and flow-cytometric analysis of lymphocyte homing and cell proliferation markers demonstrated that cell trafficking to GALT and not local proliferation contributed to CD4+ T-cell restoration. Evaluation of jejunal biopsy samples from long-term HIV-1-infected nonprogressors showed maintenance of normal CD4+ T-cell levels in both GALT and peripheral blood. Our results demonstrate that near-complete restoration of mucosal immune system can be achieved by initiating HAART early in HIV-1 infection. Monitoring of the restoration and/or maintenance of CD4 + T cells in GALT provides a more accurate assessment of the efficacy of antiviral host immune responses as well as HAART.

Original languageEnglish (US)
Pages (from-to)11708-11717
Number of pages10
JournalJournal of Virology
Volume77
Issue number21
DOIs
StatePublished - Nov 2003

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Highly Active Antiretroviral Therapy
Lymphoid Tissue
Human immunodeficiency virus 1
HIV-1
digestive system
T-lymphocytes
T-Lymphocytes
therapeutics
Infection
infection
Virus Diseases
biopsy
Maintenance
tissues
Biopsy
Gene Flow
blood
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Transcriptome

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Severe CD4+ T-Cell Depletion in Gut Lymphoid Tissue during Primary Human Immunodeficiency Virus Type 1 Infection and Substantial Delay in Restoration following Highly Active Antiretroviral Therapy",
abstract = "Gut-associated lymphoid tissue (GALT) harbors the majority of T lymphocytes in the body and is an important target for human immunodeficiency virus type 1 (HIV-1). We analyzed longitudinal jejunal biopsy samples from HIV-1-infected patients, during both primary and chronic stages of HIV-1 infection, prior to and following the initiation of highly active antiretroviral therapy (HAART) to determine the onset of CD4+ T-cell depletion and the effect of HAART on the restoration of CD4+ T cells in GALT. Severe depletion of intestinal CD4+ T cells occurred during primary HIV-1 infection. Our results showed that the restoration of intestinal CD4+ T cells following HAART in chronically HIV-1-infected patients was substantially delayed and incomplete. In contrast, initiation of HAART during early stages of infection resulted in near-complete restoration of intestinal CD4+ T cells, despite the delay in comparison to peripheral blood CD4+ T-cell recovery. DNA microarray analysis of gene expression profiles and flow-cytometric analysis of lymphocyte homing and cell proliferation markers demonstrated that cell trafficking to GALT and not local proliferation contributed to CD4+ T-cell restoration. Evaluation of jejunal biopsy samples from long-term HIV-1-infected nonprogressors showed maintenance of normal CD4+ T-cell levels in both GALT and peripheral blood. Our results demonstrate that near-complete restoration of mucosal immune system can be achieved by initiating HAART early in HIV-1 infection. Monitoring of the restoration and/or maintenance of CD4 + T cells in GALT provides a more accurate assessment of the efficacy of antiviral host immune responses as well as HAART.",
author = "Moraima Guadalupe and Elizabeth Reay and Sumathi Sankaran-Walters and Prindiville, {Thomas P} and Jason Flamm and Andrew McNeil and Satya Dandekar",
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T1 - Severe CD4+ T-Cell Depletion in Gut Lymphoid Tissue during Primary Human Immunodeficiency Virus Type 1 Infection and Substantial Delay in Restoration following Highly Active Antiretroviral Therapy

AU - Guadalupe, Moraima

AU - Reay, Elizabeth

AU - Sankaran-Walters, Sumathi

AU - Prindiville, Thomas P

AU - Flamm, Jason

AU - McNeil, Andrew

AU - Dandekar, Satya

PY - 2003/11

Y1 - 2003/11

N2 - Gut-associated lymphoid tissue (GALT) harbors the majority of T lymphocytes in the body and is an important target for human immunodeficiency virus type 1 (HIV-1). We analyzed longitudinal jejunal biopsy samples from HIV-1-infected patients, during both primary and chronic stages of HIV-1 infection, prior to and following the initiation of highly active antiretroviral therapy (HAART) to determine the onset of CD4+ T-cell depletion and the effect of HAART on the restoration of CD4+ T cells in GALT. Severe depletion of intestinal CD4+ T cells occurred during primary HIV-1 infection. Our results showed that the restoration of intestinal CD4+ T cells following HAART in chronically HIV-1-infected patients was substantially delayed and incomplete. In contrast, initiation of HAART during early stages of infection resulted in near-complete restoration of intestinal CD4+ T cells, despite the delay in comparison to peripheral blood CD4+ T-cell recovery. DNA microarray analysis of gene expression profiles and flow-cytometric analysis of lymphocyte homing and cell proliferation markers demonstrated that cell trafficking to GALT and not local proliferation contributed to CD4+ T-cell restoration. Evaluation of jejunal biopsy samples from long-term HIV-1-infected nonprogressors showed maintenance of normal CD4+ T-cell levels in both GALT and peripheral blood. Our results demonstrate that near-complete restoration of mucosal immune system can be achieved by initiating HAART early in HIV-1 infection. Monitoring of the restoration and/or maintenance of CD4 + T cells in GALT provides a more accurate assessment of the efficacy of antiviral host immune responses as well as HAART.

AB - Gut-associated lymphoid tissue (GALT) harbors the majority of T lymphocytes in the body and is an important target for human immunodeficiency virus type 1 (HIV-1). We analyzed longitudinal jejunal biopsy samples from HIV-1-infected patients, during both primary and chronic stages of HIV-1 infection, prior to and following the initiation of highly active antiretroviral therapy (HAART) to determine the onset of CD4+ T-cell depletion and the effect of HAART on the restoration of CD4+ T cells in GALT. Severe depletion of intestinal CD4+ T cells occurred during primary HIV-1 infection. Our results showed that the restoration of intestinal CD4+ T cells following HAART in chronically HIV-1-infected patients was substantially delayed and incomplete. In contrast, initiation of HAART during early stages of infection resulted in near-complete restoration of intestinal CD4+ T cells, despite the delay in comparison to peripheral blood CD4+ T-cell recovery. DNA microarray analysis of gene expression profiles and flow-cytometric analysis of lymphocyte homing and cell proliferation markers demonstrated that cell trafficking to GALT and not local proliferation contributed to CD4+ T-cell restoration. Evaluation of jejunal biopsy samples from long-term HIV-1-infected nonprogressors showed maintenance of normal CD4+ T-cell levels in both GALT and peripheral blood. Our results demonstrate that near-complete restoration of mucosal immune system can be achieved by initiating HAART early in HIV-1 infection. Monitoring of the restoration and/or maintenance of CD4 + T cells in GALT provides a more accurate assessment of the efficacy of antiviral host immune responses as well as HAART.

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