The ability of the CD300a inhibitory receptor to modulate immune cell functions and its involvement in the pathogenesis of many diseases has aroused a great interest in this molecule. Within human CD4+ T lymphocytes from healthy donors, the inhibitory receptor CD300a is differentially expressed among different T helper subsets. However, there are no data about the expression and regulation of CD300a receptor on CD4+ T cells from human immunodeficiency virus (HIV)-1-infected patients. The objective of this study was to investigate the expression of CD300a on CD4+ T cells from HIV-infected patients on suppressive combined antiretroviral therapy (cART) and cART naïve patients. Our results have demonstrated that the expression levels of this inhibitory receptor were higher on CD4+ T cells from HIV-1 infected subjects compared with healthy donors, and that cART did not reverse the altered expression of CD300a receptor in these patients. We have observed an increase of CD300a expression on both PD1+CD4+ and CD38+CD4+ T cells from HIV-1 infected people. Interestingly, a triple positive (CD300a+PD1+CD38+) subset was expanded in naïve HIV-1 infected patients, while it was very rare in healthy donors and patients on cART. Finally, we found a negative correlation of CD300a expression on CD4+ T lymphocytes and some markers associated with HIV-1 disease progression. Thus, our results show that HIV-1 infection has an impact in the regulation of CD300a inhibitory receptor expression levels, and further studies will shed light into the role of this cell surface receptor in the pathogenesis of HIV infection.

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 ...

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