Helios expressing regulatory T cells are correlated with decreased IL-2 producing CD8 T cells and antibody diversity in Mozambican individuals living chronically with HIV-1.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) causes impairment of T and B cell responses, which begins during the acute phase of infection and is not completely restored by antiretroviral treatment. Regulatory T cell (Tregs) can improve overall disease outcome by controlling chronic inflammation but may also suppress beneficial HIV-1 specific immune responses. We aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response in Mozambican people living chronically with HIV-1 (PLWH-C). RESULTS: In PLWH-C, the proportion of total Tregs was positively correlated with the proportion of IL-2+CD4 T cells (r = 0.647; p = 0.032) and IL-2+IFNγ+CD8 T cells (r = 0.551; p = 0.014), while the proportions of Helios+Tregs correlated inversely with levels of IL-2+CD8 T cells (r = - 0.541; p = 0.017). Overall, PLWH-C, with (82%) or without virologic suppression (64%), were seronegative for at least HIV-1 p31, gp160 or p24, and the breadth of antibody responses was positively correlated with proportions of CD38+HLA-DR+CD8 T cells (r = 0.620; p = 0.012), viral load (r = 0.452; p = 0.040) and inversely with absolute CD4 T cells count (r = - 0.481; p = 0.027). Analysis of all individuals living HIV-1 showed that the breadth of HIV-1 antibody responses was inversely correlated with the proportion of Helios+Tregs (r = - 0.45; p = 0.02). CONCLUSION: Among Mozambican people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of Helios+Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.

Caracterização Hemato-linfocitária em Crianças Infectadas por Malária / Hematolymphocyte Characterization in Malaria Infected Children

Introdução: Moçambique é um dos países endémicos à malária. Em 2011, a estimativa de prevalência desta doença era de 40­80% em crianças dos 2­9 anos e 90% em crianças menores de 5 anos. Estas altas prevalências podem ser devido à dificuldade das crianças em desenvolverem uma resposta imune eficaz. São necessários mais estudos para entender a resposta imune nestas crianças. Este estudo teve como objectivo descrever as características imuno-hematológicas em crianças menores de 15 anos infectadas por Plasmodium falciparum. Metodologia: Foram recrutadas crianças de 2-15 anos, infectadas por P. falciparum. Em cada criança, cujo tutor legal consentiu que participasse no estudo, colheu-se 5 ml de sangue venoso para um tubo com anticoagulante K3EDTA. O sangue foi usado para a contagem automática de células por citometria de fluxo. Os resultados foram agrupados por idade, dos 2-8 anos e 9-15 anos. Resultados: Das 50 crianças incluídas no estudo, 84% tinham idades entre os 2-8 anos, 70% do sexo masculino e 4% com serologia positiva para HIV. O nível de hemoglobina foi mais elevado no grupo de 9-15 anos (10,3g/dL) em relação ao grupo de 2-8 anos (8,7g/dL). A contagem absoluta de linfócitos T-CD4 foi maior no grupo de 2-8 anos (819 cél./µl). A activação celular não apresentou diferenças entre os grupos. Conclusão: A maioria dos casos de malária e anemia aguda foi observada em crianças dos 2 aos 8 anos, predominantemente do sexo masculino. Os valores absolutos de linfócitos foram mais elevados nas crianças dos 2-8 anos, mas os valores percentuais linfocitários não diferiram entre os grupos.

Introduction: Mozambique is one of the endemic countries to malaria. In 2011, the estimated prevalence of this disease was 40­80% in children aged from 2­9 years and 90% in children under 5 years. These high rates may be due to the difficulty of children in building an effective immune response. Further studies are needed to understand the immune response mounted by children in the presence of Plasmodium. This study aimed to describe the immuno-haematological characteristics of children under 15 years infected with Plasmodium falciparum. Methodology: Children aged from 2-15 years, infected with P. falciparum, were recruited for the study. In each child, whose legal guardian consented to take part of the study, was collected 5 ml of venous blood to a K3EDTA anticoagulant tube. The samples were tested using automatic full blood cell counting and flow cytometry. The results were grouped by age, 2-8 years and 9-15 years. Results: From the 50 children included in the study, 84% were aged 2-8 years, 70% were male and 4% were HIV positive. The haemoglobin level was higher in the 9-15 year old group (10.3g/dL) compared to the 2-8 year old group (8.7g/dL). The absolute T-CD4 lymphocytes levels were higher in the 2-8 year old group (819 cells/µl). The T-CD8 lymphocytes activations levels were similar in both groups. Conclusion: The majority of the children attended in the Paediatric Emergency who diagnosed malaria were 2 to 8 years old. These children were predominantly male and presented acute anaemia. The absolute T-CD4 and T-CD8 lymphocytes levels were higher in children aged 2-8 years, but the percentage levels of lymphocytes did not differ between groups.

Performance Evaluation of the MyT4 Technology for Determining ART Eligibility.

BACKGROUND: In resource-limited countries, CD4 T-cell (CD4) testing continues to be used for determining antiretroviral therapy (ART) initiation eligibility and opportunistic infection monitoring. To support expanded access to CD4 testing, simple and robust technologies are necessary. We conducted this study to evaluate the performance of a new Point-of-Care (POC) CD4 technology, the MyT4, compared to conventional laboratory CD4 testing. METHODS: EDTA venous blood from 200 HIV-positive patients was tested in the laboratory using the MyT4 and BD FACSCalibur™. RESULTS: The MyT4 had an r2 of 0.82 and a mean bias of 12.3 cells/µl. The MyT4 had total misclassifications of 14.7% and 8.8% when analyzed using ART eligibility thresholds of 350 and 500 cells/µl, respectively. CONCLUSIONS: We conclude that the MyT4 performed well in classifying patients using the current ART initiation eligibility thresholds in Mozambique when compared to the conventional CD4 technology.

Performance Evaluation of the MyT4 Technology for Determining ART Eligibility

Background In resource-limited countries, CD4 T-cell (CD4) testing continues to be used for determining antiretroviral therapy (ART) initiation eligibility and opportunistic infection monitoring. To support expanded access to CD4 testing, simple and robust technologies are necessary. We conducted this study to evaluate the performance of a new Point-of-Care (POC) CD4 technology, the MyT4, compared to conventional laboratory CD4 testing. Methods EDTA venous blood from 200 HIV-positive patients was tested in the laboratory using the MyT4 and BD FACSCalibur™. Results The MyT4 had an r 2 of 0.82 and a mean bias of 12.3 cells/µl. The MyT4 had total misclassifications of 14.7% and 8.8% when analyzed using ART eligibility thresholds of 350 and 500 cells/µl, respectively. Conclusions We conclude that the MyT4 performed well in classifying patients using the current ART initiation eligibility thresholds in Mozambique when compared to the conventional CD4 technology.