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

Joana Vitallé,Francisco Borrego,Iñigo Terrén,Ane Orrantia,Manuel Leal,Leire Gamboa-Urquijo,Olatz Zenarruzabeitia,Miguel Genebat,Laura Tarancón-Díez,Ezequiel Ruiz-Mateos

doi:10.1038/s41598-020-63025-4

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 Gag HIV-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.

Highlights

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature
The CD300a inhibitory receptor has been related to numerous immunological processes and diseases[18,21] and its expression is known to be modulated on B and CD4+ T lymphocytes from chronically human immunodeficiency virus (HIV)-1+ patients[24,38]
The first step was to determine the expression of CD300a receptor on CD8+ T cell subsets from HIV-1+ individuals naïve for combined antiretroviral therapy (cART) and on cART compared with HIV negative donors

Summary

Introduction

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. 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). The ability of human CD300a molecule to inhibit immune processes has been demonstrated in several cell types, including TCR-mediated signalling on CD4+ T lymphocytes[22,23], B cell receptor (BCR)-mediated signalling[24], FcεRI and FcRγIIa-mediated signalling on basophils and mast cells[25,26] and on neutrophils[27], respectively, and NK cell-mediated cytotoxicity and cytokine production[28,29,30,31]. A CD4+ T cell subset co-expressing CD300a, PD1 and CD38 was expanded in naïve HIV-1+ individuals, which was found in very low numbers in HIV negative donors and in patients under cART38. We have recently reported that CD300a is up-regulated on CD56neg NK cells from untreated HIV-1+ subjects and importantly, we demonstrated the capacity of CD300a to inhibit antibody-dependent NK cell degranulation and cytokine production in HIV-1+ individuals[31]

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Conclusion