Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection.

BACKGROUND: The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation. OBJECTIVES: We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. We also assessed phenotypic differences between CD31+ and CD31- subsets in memory and terminally differentiated (TEMRA) CD4+ and CD8 + T cells. METHODS: Forty-one individuals with untreated HIV infection and 34 non-HIV-infected controls were included in the study. We compared the expression of CD31 in CD4+ and CD8 + T cells across stages of differentiation in the two study groups by flow cytometry. We also analyzed the expression of CD57 (a marker of senescence), Ki67 (a marker of cycling cells), PD-1 (a marker of exhaustion), and CD38/HLA-DR (a marker of immune activation) on memory and TEMRA CD31+ and CD31- T cells. RESULTS: CD31 expression was significantly higher in CD8 + T cells than in CD4 + T cells, measured as frequency, absolute numbers and median fluorescence intensity (MFI), in both study groups (p < 0.0001 in all cases). Intermediate differentiation subsets of CD4+ and CD8 + T cells expressed higher levels of CD31 in the context of HIV infection (p < 0.001 in all cases). CD31 expression frequency decreased with cellular differentiation of CD4+ and CD8 + T cells in both groups, but this decrease was steeper in individuals without HIV infection (CD4+: p < 0.001 and CD8+: p < 0.0001). As expected, memory and TEMRA CD4+ and CD8 + T cells expressed significantly higher levels of CD57, PD-1, Ki67 and CD38/HLA-DR in HIV-infected compared to non-HIV-infected individuals (p < 0.01 in all cases). CD31 expression was associated with lower activation of memory (but not TEMRA) CD4 + T cells in non-HIV-infected persons, an effect not observed in the HIV-infected group. CD31 expression on memory CD8 + T cells of HIV-infected individuals was associated higher levels of PD-1 (p = 0.0019) and CD38/HLADR (p = 0.0345), and higher PD-1 expression on CD8 + TEMRA (p = 0.0024), an effect not observed in non-HIV-infected individuals. CONCLUSION: In the context of HIV-associated chronic immune activation, specifically on memory CD8 + T cells, CD31 expression was associated with higher PD-1 and CD38/HLA-DR co-expression, suggesting that CD31 expression may result from an insufficient attempt to contain T cell exhaustion and activation. CD31-targeted therapies may contribute to modulate these cellular responses.

Influenza: forecast for a pandemic.

Recently, great speculation about a possible influenza pandemic has been made. However, the facts supporting the possibility of this threat are less discussed. During the last decade highly pathogenic strains of avian influenza virus, including the H5N1 subtype, crossed the species barriers from birds to humans and caused fatal disease. The Z strain of H5N1 subtype is characterized by pathogenicity to a larger number of animal species and by resistance to the older class of antiviral drugs. At present, two out of three general conditions for the onset of a pandemic have been met; namely, the emergence of a new virus and its ability to replicate in humans causing serious illness. Should the virus achieve efficient human-to-human transmission, the next influenza pandemic might occur. This review addresses these biological and epidemiological aspects of influenza in the context of history and characteristics of previous epidemics, as well as concrete actions that can be undertaken considering current understanding of influenza pathogenesis, treatment, and control possibilities.