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
Open accessAbstract
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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Organ-specific non-peripheral cells with tissue-homing markers can transiently appear in blood cell preparations.
“In these blood cell preparations, organ-specific non-peripheral cells with tissue-homing markers can also transiently appear. 16-20”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [18]
The Results report that peripheral blood CD4+ T cells expressed integrin β7, a marker involved in homing to the intestinal mucosa. They do not establish that these cells originated in an organ or appeared only transiently in blood cell preparations; the proposed trafficking direction is from the periphery to the gut. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIt is known that especially integrin a4b7-expressing cells are predominantly infected and depleted during the early infection phases, with a rather poor recovery during ART.
“It is known that especially integrin a 4 b 7 -expressing cells are predominantly infected and depleted during the early infection phases, with a rather poor recovery during ART. 18,20”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [18]
The Results (page not specified) show severe intestinal CD4+ T-cell depletion during primary HIV-1 infection and delayed, incomplete recovery with HAART begun during chronic infection. They measure integrin β7 expression during HAART, but do not show that α4β7-expressing cells are preferentially infected or depleted, or that this specific subset recovers poorly. The Results also report near-complete intestinal CD4+ T-cell restoration when HAART began during primary infection. (LLM, conf=0.88)
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- Authors
- Guadalupe, M., Reay, E., Sankaran, S., Prindiville, T., Flamm, J., McNeil, A., & Dandekar, S.
- Affiliations
- University of California, Davis (US)
- Departments of Medical Microbiology & Immunology
- The Permanente Medical Group Inc.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2003-11
- Volume
- 77
- Issue
- 21
- Pages
- 11708-11717
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC229357
- OpenAlex
- W2076120354
- Cited by
- 866
- References
- 24
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 11 · 2023: 14 · 2022: 23 · 2021: 27 · 2020: 21 · 2019: 26 · 2018: 26 · 2017: 32 · 2016: 42 · 2015: 45 · 2014: 48 · 2013: 62 · 2012: 60
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 61297, R01DK061297)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Keywords
- HIV-1 infection, CD4+ T cell depletion, gut-associated lymphoid tissue, highly active antiretroviral therapy, CD4+ T cell recovery, jejunal biopsy, lymphocyte homing, nonprogressors, gene expression profiling, early treatment initiation
- MeSH terms
- Adult, Cell Movement, Chronic Disease, Female, Flow Cytometry, Humans, Immunohistochemistry, Jejunum, Lymphocyte Activation, Lymphoid Tissue, Male, Middle Aged, Time Factors, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, CD8-Positive T-Lymphocytes, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active
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