The aim of this study was to determine the patterns of change in body fat and metabolic parameters in a South African cohort on a first line ART regimen containing stavudine. Fasting lipogram, blood ...glucose and insulin levels, CD4 cell count, viral load, BMI, waist-to-hip ratio (WHR), and skinfold thickness at the triceps, scapula, and iliac crest were measured before starting ART in 42 (27 female) subjects. Repeat measurements were performed at four monthly intervals for 2 years. Lipodystrophy was diagnosed using patient perception and assessment by a physician. At baseline, subjects who went on to develop lipodystrophy (LD group) were fatter and had higher skinfold thickness at all three sites and higher insulin levels than subjects who never developed lipodystrophy (NLD group). The WHR increased to a greater extent while hip circumference and tricep skinfolds fell more significantly in the LD than NLD group. Triglyceride and cholesterol levels increased significantly in both groups while lactate and glucose levels increased more and insulin levels increased less in the LD than the NLD group. Neither viral load nor CD4 count differed between the groups during the study. Viral load correlated positively with insulin levels at baseline. Thus, lipodystrophy in the South African population is characterized by a higher BMI before initiation of ART and lipoatrophy of the arms and hips, lipohypertrophy of the waist, and increased lactate production. When compared to the NLD group, the LD subjects display attenuated insulin secretory output in response to a higher weight gain.
The semaphorin and plexin family of ligand and receptor proteins provides important axon guidance cues required for development. Recent studies have expanded the role of semaphorins and plexins in ...the regulation of cardiac, circulatory and immune system function. Within the immune system, semaphorins and plexins regulate cell-cell interactions through a complex network of receptor and ligand pairs. Immune cells at different stages of development often express multiple semaphorins and plexins, leading to multivariate interactions, involving more than one ligand and receptor within each functional group. Because of this complexity, the significance of semaphorin and plexin regulation on individual immune cell types has yet to be fully appreciated. In this work, we examined the regulation of T cells by semaphorin 6D. Both in vitro and in vivo T cell stimulation enhanced semaphorin 6D expression. However, semaphorin 6D was only expressed by a majority of T cells during the late phases of activation. Consequently, the targeted disruption of semaphorin 6D receptor-ligand interactions inhibited T cell proliferation at late but not early phases of activation. This proliferation defect was associated with reduced linker of activated T cells protein phosphorylation, which may reflect semaphorin 6D regulation of c-Abl kinase activity. Semaphorin 6D disruption also inhibited expression of CD127, which is required during the multiphase antigen-presenting cell and T cell interactions leading to selection of long-lived lymphocytes. This work reveals a role for semaphorin 6D as a regulator of the late phase of primary immune responses.
The semaphorin and plexin family of ligand and receptor proteins provides important axon guidance cues required for development. Recent studies have expanded the role of semaphorins and plexins in ...the regulation of cardiac, circulatory and immune system function. Within the immune system, semaphorins and plexins regulate cell-cell interactions through a complex network of receptor and ligand pairs. Immune cells at different stages of development often express multiple semaphorins and plexins, leading to multivariate interactions, involving more than one ligand and receptor within each functional group. Because of this complexity, the significance of semaphorin and plexin regulation on individual immune cell types has yet to be fully appreciated. In this work, we examined the regulation of T cells by semaphorin 6D. Both in vitro and in vivo T cell stimulation enhanced semaphorin 6D expression. However, semaphorin 6D was only expressed by a majority of T cells during the late phases of activation. Consequently, the targeted disruption of semaphorin 6D receptor-ligand interactions inhibited T cell proliferation at late but not early phases of activation. This proliferation defect was associated with reduced linker of activated T cells protein phosphorylation, which may reflect semaphorin 6D regulation of c-Abl kinase activity. Semaphorin 6D disruption also inhibited expression of CD127, which is required during the multiphase antigen-presenting cell and T cell interactions leading to selection of long-lived lymphocytes. This work reveals a role for semaphorin 6D as a regulator of the late phase of primary immune responses.
PDF
