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

Abstract

HIV infection induces remarkable expansion of CD8CD28CD127CD39 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.

CD8+CD28- T cells: not only age-related cells but a subset of regulatory T cells

“…3,10,11 Currently, CD8+CD28-T cells contribute to the prediction of prognosis in inflammatory disease; for example, the frequency of a CD8+CD28-T-cell subset in the circulation may serve as new marker of response to antiretroviral therapy in HIV, and the CD8+CD28 +/CD8+CD28-T-cell ratio can sensitively predict the outcome for IBD patients. 9,12 These results support the idea that CD8+CD28-T cells may control the occurrence and progression of inflammatory disease. Thus, strategies to increase the number or immunosuppressive capacity of CD8+CD28-T cells might be an effective means of treating these diseases.…”

“…3 Increases of CD8 +CD28-T cells are also observed in chronic viral infections, such as hepatitis C virus (HCV), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) or human immunodeficiency virus (HIV) infections. 3,9 CD8+CD28-T cells also expand after bone morrow or solid organ transplantation and may serve as a mechanism of primary tolerance in transplantation, yielding better graft acceptance and stabilizing graft function, and their expansion is associated with a reduced occurrence of rejection. 3,10 In autoimmune diseases, such as type 1 diabetes mellitus and multiple sclerosis, 3 the CD8+CD28-T-cell population is significantly smaller than that seen in healthy controls.…”

AIDS and COVID-19 are two diseases separated by a common lymphocytopenia

“…In our HIV patients the CD8+ T cells are slightly increased, with respect to the normal value. In this regard, a remarkable expansion of CD8+CD28-CD127loCD39+ Treg cells, that correlates with HIV viremia, has been previously reported [15]. The total number of these cells correlates also with the clinical course of the disease and, in particular, with signs of chronic immune cell activation and with immunode ciency events.…”

Future prospects for CD8+ regulatory T cells in immune tolerance

“…In addition, the methylation status of FOXP3 in human CD8 + Tregs showed an intermediate level of demethylation compared to one of the CD4 + Tregs for some locus of the FOXP3 gene. 2,10 Indeed, using a combination of these markers to identify CD8 + Tregs, their suppressive action has been demonstrated in autoimmune diseases such as in the experimental autoimmune encephalomyelitis model, [11][12][13] multiple sclerosis, [14][15][16] systemic lupus erythematosus (SLE) 17,18 and primary biliary cirrhosis, 19 in infection in humans with mycobacteria, human immunodeficiency virus or epstein-barr virus, [20][21][22][23] in cancer in humans and mice [24][25][26] or in transplantation in humans, mice and rats. 3 In contrast, in a rat model of transplantation tolerance following costimulation blockade inducing in vivo CD8 + Tregs, FOXP3 was not upregulated, 4 nor was it in a model of tolerance in rat using donor antigen therapy.…”

“…8,9 Other surface markers were also suggested and among the most frequently used CD25, CD127, GITR, CD39, Lag3, and CTLA-4 that are used in different contexts and different species to identify CD8 + Tregs and analyze their suppressive activity in vitro and in vivo in autoimmune diseases, immune reactions to non-self, cancer and materno-fetal tolerance. 2,10 Indeed, using a combination of these markers to identify CD8 + Tregs, their suppressive action has been demonstrated in autoimmune diseases such as in the experimental autoimmune encephalomyelitis model, [11][12][13] multiple sclerosis, [14][15][16] systemic lupus erythematosus (SLE) 17,18 and primary biliary cirrhosis, 19 in infection in humans with mycobacteria, human immunodeficiency virus or epstein-barr virus, [20][21][22][23] in cancer in humans and mice [24][25][26] or in transplantation in humans, mice and rats. 3,4,[27][28][29][30][31][32] was used to identify antibody-suppressor FOXP3 − CD8 + cells in mice and essential in their function of suppression of humoral immunity, reducing germinal center B cells and CD4 + T follicular helper cells in the context of hepatocyte transplantation.…”