Follicular Immune Landscaping Reveals a Distinct Profile of FOXP3CD4 T Cells in Treated Compared to Untreated HIV.

Follicular helper CD4 T cells (T) are a major cellular pool for the maintenance of the HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with the relevant computational tools, to investigate F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral-treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls.

Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIV infection.

Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIV infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs.

Neutralization activity in chronic HIV infection is characterized by a distinct programming of follicular helper CD4 T cells.

A subset of people living with HIV (PLWH) can produce broadly neutralizing antibodies (bNAbs) against HIV, but the lymph node (LN) dynamics that promote the generation of these antibodies are poorly understood. Here, we explored LN-associated histological, immunological, and virological mechanisms of bNAb generation in a cohort of anti-retroviral therapy (ART)-naïve PLWH. We found that participants who produce bNAbs, termed neutralizers, have a superior LN-associated B cell follicle architecture compared with PLWH who do not.

HIV infection is associated with compromised tumor microenvironment adaptive immune reactivity in Hodgkin lymphoma.

The impact of HIV infection on the tumor microenvironment (TME) of classic Hodgkin lymphoma (cHL), one of the most common comorbidities after HIV infection, is not well understood. Here, we have used multiplexed immunofluorescence and spatial transcriptomic analysis to dissect the impact of viral infections (Epstein-Barr virus [EBV] and HIV/EBV) on cHL TME. HIV-EBV+ cHL TME was characterized by higher cell densities of CD8high T cells coexpressing inhibitory receptors (PD-1 and TIGIT), macrophage subsets, and an in situ inflammatory molecular profile associated with increased expression of T-cell receptor (TCR) and B-cell receptor cell signaling pathways than HIV-EBV- cHL TME.

RAIN: machine learning-based identification for HIV-1 bNAbs.

Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoires is still lacking. Here, we develop a straightforward computational method for the Rapid Automatic Identification of bNAbs (RAIN) based on machine learning methods.