CD8+CD28−CD127loCD39+ regulatory T-cell expansion: A new possible pathogenic mechanism for HIV infection?

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Abstract

Background:

HIV-associated immunodeficiency is related to loss of CD4+ T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4+ T cells/μL. CD8+CD28−CD127loCD39+ T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients.

Objectives:

We sought to analyze the frequency of CD8+CD28−CD127loCD39+ Treg cells in the circulation of HIV-infected patients.

Methods:

The frequency of circulating CD8+CD28−CD127loCD39+ Treg cells was analyzed and correlated with viral load and CD4+ T-cell counts/percentages in 93 HIV-1–infected patients subdivided as follows: naive (n = 63), elite controllers (n = 19), long-term nonprogressors (n = 7), and HIV-infected patients affected by tumor (n = 4). The same analyses were performed in HIV-negative patients with cancer (n = 53), hepatitis C virus–infected patients (n = 17), and healthy donors (n = 173).

Results:

HIV-infected patients had increased circulating levels of functional CD8+CD28−CD127loCD39+ Treg cells. These cells showed antigen specificity against HIV proteins. Their frequency after antiretroviral therapy (ART) correlated with HIV viremia, CD4+ T-cell counts, and immune activation markers, suggesting their pathogenic involvement in AIDS- or non–AIDS-related complications. Their increase after initiation of ART heralded a lack of virologic or clinical response, and hence their monitoring is clinically relevant.

Conclusion:

HIV infection induces remarkable expansion of CD8+CD28−CD127loCD39+ Treg cells, the frequency of which correlates with both clinical disease and signs of chronic immune cell activation. Monitoring their frequency in the circulation is a new marker of response to ART when effects on viremia and clinical response are not met.

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