Objective: Correlation between GALT homing markers on lym-phocytes and the low blood CD4 T-cell reconstitution in immuno-logical nonresponders (INRs) has been studied. Design: Thirty-one INRs, 19 immunological responders (IRs), and 12 noninfected controls were enrolled in this study. INRs were defined by an undetectable plasma viral load RNA less than 40 copies per milliliter and CD4 + T-cell count ,500 cells per cubic milliliter in at least 3 years. Methods: A complete peripheral and mucosal lymphocyte immu-nophenotyping was performed on these patients with a focus on the CCR9, CCR6, and a4b7 gut-homing markers. Results: A highly significant upregulation of a4b7 on INRs peripheral lymphocytes compared with that of IRs has been observed. This upregulation impacts different lymphocyte subsets namely CD4 + , CD8 + , and B lymphocytes. The frequency of b7 + Th17 and Treg cells are increased compared with IRs and healthy controls. The frequency of b7 + CD8 + T cells in the blood is negatively correlated with integrated proviral DNA in rectal lymphoid cells in contrast to b7 + CD4 + T cells associated with HIV integration. Conclusions: Alteration of lymphocyte homing abilities would have deleterious effects on GALT reconstitution and could participate to HIV reservoir constitution. These results emphasize the great interest to consider a4b7-targeted therapy in INR patients to block homing of lymphocytes and/or to directly impair gp120-a4b7 interactions.
Background: Cell-to-cell HIV transmission requires cellular contacts that may be in part mediated by the integrin leukocyte function antigen (LFA)-1 and its ligands intercellular adhesion molecule (ICAM)-1, -2 and -3. The role of these molecules in free virus infection of CD4 T cells or in transinfection mediated by dendritic cells (DC) has been previously described. Here, we evaluate their role in viral transmission between different HIV producing cells and primary CD4 T cells.
Highlights► Current influenza vaccines do not generate heterologous protection. ► Targeting internal influenza antigens may confer cross protection. ► We tested Adenovirus and MVA vectored NP and M1 in chickens. ► Heterologous prime-boost resulted in earlier cessation of viral shedding.
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