Recent studies have indicated that Treg contribute to the HIV type 1 (HIV-1)-related immune pathogenesis. However, it is not clear whether T cells with suppressive properties reside within the HIV-1-specific T-cell population. Here, PBMC from HIV-1-infected individuals were stimulated with a 15-mer Gag peptide pool, and HIV-1-specific T cells were enriched by virtue of their secretion of IL-10 or IFN-gamma using immunomagnetic cell-sorting. Neither the IL-10-secreting cells nor the IFN-gamma-secreting cells expressed the Treg marker FOXP3, yet the IL-10-secreting cells potently suppressed anti-CD3/CD28-induced CD4(+) as well as CD8(+) T-cell proliferative responses. As shown by intracellular cytokine staining, IL-10- and IFN-gamma-producing T cells represent distinct subsets of the HIV-1-specific T cells. Our data collectively suggest that functionally defined HIV-1-specific T-cell subsets harbor potent immunoregulatory properties that may contribute to HIV-1-associated T-cell dysfunction.
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http://dx.doi.org/10.1002/eji.200839002 | DOI Listing |
Med Microbiol Immunol
December 2024
Immunology Section, Molecular Immuno-Biology Laboratory, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Introduction: While the general immune response to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is well-understood, the long-term effects of Human Immunodeficiency Virus-1/Severe Acute Respiratory Syndrome-Coronavirus-2 (HIV-1/SARS-CoV-2) co-infection on the immune system remain unclear. This study investigates the immune response in people with HIV-1 (PWH) co-infected with SARS-CoV-2 to understand its long-term health consequences.
Methods: A retrospective longitudinal study of PWH with suppressed viral load and SARS-CoV-2 infection was conducted.
J Exp Med
November 2024
Ragon Institute of MGH, MIT and Harvard , Cambridge, MA, USA.
Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses.
View Article and Find Full Text PDFCell Rep Med
October 2024
Department of Medicine, University of California San Francisco, San Francisco, CA 94110, USA.
Key HIV cure strategies involve reversing immune dysfunction and limiting the proliferation of infected T cells. We evaluate the safety of sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in people with HIV (PWH) and study the impact of sirolimus on HIV-1 reservoir size and HIV-1-specific immunity in a single-arm study of 20 weeks of treatment in PWH on antiretroviral therapy (ART). Sirolimus treatment does not impact HIV-1-specific CD8 T cell responses but leads to a significant decrease in CD4 T cell-associated HIV-1 DNA levels at 20 weeks of therapy in the primary efficacy population (n = 16; 31% decline, p = 0.
View Article and Find Full Text PDFNat Med
December 2024
Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies. A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound. Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2.
View Article and Find Full Text PDFJ Infect Dis
September 2024
Division of International Collaboration Research and Tokyo Joint Laboratory, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto/Tokyo, Japan.
HLA-B*58:01 and HLA-B*57 are protective alleles against HIV-1 subtype B or C infection whereas these HLA alleles have not been reported as protective in HIV-1 subtype AE infection. Although HLA-B*58:01-restricted and HLA-B*57-restricted HIV-1-specific CD8+ T cells have been thoroughly analyzed in subtype B or C infection, they have only been partially analyzed in subtype AE infection. We identified six HLA-B*58:01-restricted subtype AE epitopes in Vietnamese individuals infected with subtype AE.
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