Immune development in HIV-exposed uninfected children born to HIV-infected women

ABSTRACT Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1β levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.

Assessment of the role of M-CSF in expansion of CD 14 + CD 16 + blood monocytes in patients undergoing haemodialysis

The immunodeficiency of patients with chronic renal failure [CRF] is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is a key factor in these immunological disorders. A normal subpopulation of blood monocytes coexpressing CD 16 antigen and low level of CD 14 antigen [CD 14+ CD16+] has recently been identified. In this study, we measured the plasma levels of some relevant haemopoietic growth factors and cytokines in 32 patients suffering from CRF who were undergoing haemodialysis and 12 healthy controls, using an ELISA technique. The plasma levels of macrophage - colony stimulating factor [M- CSF] were significantly increased in patients compared to controls [p < 0.001], while the increase in granulocyte macrophage colony stimulating factor [GM - CSF] and interleukin 10 [IL - 10] was insignificant [p > 0.05]. We also examined the immunophenotype of blood monocytes in haemodialysed patients using two - colour immunofluorescence flow cytometry. A significant increase in the percentage and absolute number of CD 14+ CD 16+ monocytes was noted in patients compared to controls [p<0.00l]. On the other hand, the percentage of CD 14++ CD 16- regular monocytes was slightly but significantly decreased [p < 0.01], although their absolute number did not differ significantly [p > 0.05]. Significant correlation was detected between plasma levels of M - CSF and the number of CD 14+ CD 16+ monocytes.Our results suggest that increased endogenous levels of M-CSF plays a major role in the chronic activation of monocyte subpopulations and may be responsible for the expansion of CD 14+ CD 16+ blood monocytes which leads to multiple metabolic, haematologic and immunologic defects in CRF patients under haemodialysis

Granulocyte macrophage colony stimulating factor: role in induction of monocyte CD14 receptor and adhesion molecules expression in chronic liver diseases

This study included 36 chronic liver disease [CLD] patients who suffered from viral hepatitis and / or schistosomiasis and 12 age and sex matched healthy individuals who represent the control group. The study aimed at clarifying the role of rhGM-CSF on the release of sICAM-1 and sCD14 from PBMNC. According to the severity of liver disease, patients were classified to Child A, B and C groups. All patients and controls were subjected to thorough history taking and clinical examination, a full routine laboratory investigation including hemogram, liver function tests and hepatitis markers. PB mononuclear cell culture was performed to all the study groups with and without the addition of rhGM-CSF to the culture media. Afterwards, slCAM-1 and sCDl4 were measured in culture supernatant fluid using ELISA technique, Levels of sICAM-1 in culture supernatants with and without addition of rhGM-CSF showed significant progressive increase with advancement of CLD which may reflect the increase ofsICAM-1 in sera of CLD patients with progression of the disease. As well, the addition of rhGM-CSF to PBMNC culture resulted in a significant reduction of sICAM-1 level in culture supernatants in control and patients groups in comparison to its level without the addition of rhGM-CSF. There was a significant progressive increase in sCD14 level with the advancement of the disease. The increase in sCD14 level with and without addition of rhGM-CSF was significant in all patients groups in comparison to the control group. As well, the addition of rhGM-CSF to culture media led to significant reduction of sCD14 concentration in supernatants in control group and in each of the patients groups in comparison to their levels without the addition of rhGM-CSF. It can be concluded that rhGM-CSF might be considered as one of the potential future tools against defective monocyte functions in CLDs. Using rhGM-CSF to improve monocyte functions will be associated with reduction of sICAM-1 and sCD14 levels which might be implicated or contribute to liver pathology