Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Abstract

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a GagHIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response. CD8+ T cells are very important effectors in the control and clearance of viruses through several mechanisms, including granule exocytosis and cytokine production 1-3 . Many reports have shown that CD8+ T cells play a very important role in the control of viral replication during the acute phase of human immunodeficiency virus (HIV)−1 infection, contributing to the initial control of infection 1,3-7 . Thus, a large number of current studies are focused on the search of new therapies with the aim of inducing a potent and effective HIV specific CD8+ T cell response [8][9][10] .After antigen recognition and subsequent activation, CD8+ T cells up-regulate the expression of inhibitory receptors with the aim of preventing an excessive response that, if not properly regulated, could be harmful to the host 11,12 . During chronic stimulation, as for example persistent exposure to HIV antigens, CD8+ T cells became progressively dysfunctional and exhausted, and the expression of inhibitory receptors persists 13 . Exhaustion is a process characterized by a loss of proliferative capacity, differentiation and effector functions 12,14,15 . There are several inhibitory receptors that are expressed on exhausted T cells. For instance, programed cell death-1 (PD1) is known to be involved in the regulation of CD8+ T lymphocytes function during chronic HIV-1 infection and their expression correlates with disease progression 11,12,15 . In addition to the negative regulatory role of these inhibitory receptors, they also mark antigen specific T cells. For example, it has been described that PD1 on CD8+ T cells identifies the repertoire of clonally expanded tumor-reactive lymphocytes and situations of chronic inflammation, which is ...

Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

“…In other words, neonatal T cells are less polyfunctional, which could subsequently lead to less potent T cell responses (96). In a recent study on HIV-1 responses by CD8 + T cells, the results showed that HIV-1 specific adult CD8 + T cells with high frequencies of CD300a were more polyfunctional (111). These observations are in line with the difference in CD300a expression levels between adults and neonates, as described in the previous paragraph.…”

CD8+T-cell response to mutated HLA-B*35-restricted Gag HY9 and HA9 epitopes from HIV-1 variants from Medellin, Colombia

“…Gate defining the positive production of cytokines and cytotoxic molecules were combined by the boolean gating strategy as indicated in the FlowJo software. The polyfunctional profile was defined as the capacity of CD8 + T-cells to produce multiple markers simultaneously [ 23 , 24 ]. The percentage of cells exhibiting from one to six functions was analyzed as previously described using the SPICE v5.35 software [ 22 , 25 ].…”

Human IgMhiCD300a+ B Cells Are Circulating Marginal Zone Memory B Cells That Respond to Pneumococcal Polysaccharides and Their Frequency Is Decreased in People Living with HIV

“…The relevance of the CD300a molecule in several pathological conditions has been highlighted by multiple studies [ 3 , 4 , 5 , 6 , 7 ]. Among others, CD300a has been related to bacterial, parasitic, and viral infections [ 4 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. For instance, after cecal ligation and puncture peritonitis in mice, the absence of CD300a induced a more effective bacterial clearance and prolonged mice survival by increasing mast cell inflammatory response and neutrophil recruitment [ 16 , 17 ].…”

“…For instance, after cecal ligation and puncture peritonitis in mice, the absence of CD300a induced a more effective bacterial clearance and prolonged mice survival by increasing mast cell inflammatory response and neutrophil recruitment [ 16 , 17 ]. CD300a is broadly expressed on myeloid and lymphoid cells, and its expression is known to be differentially regulated depending on the cell type [ 11 , 12 , 13 , 14 , 15 , 18 , 19 , 20 , 21 , 22 , 23 ]. Regarding B cells, besides some aspects of the expression and function of CD300a on several human B cell subsets, its relevance in B cell leukemogenesis, and its potential relevance in viral infections [ 23 , 24 , 24 , 25 , 26 ], its role is not completely known.…”