Early Antiretroviral Therapy Preserves Functional Follicular Helper T and HIV-Specific B Cells in the Gut Mucosa of HIV-1-Infected Individuals

Cyril Planchais (1, 2) , Laurent Hocqueloux (3) , Clara Ibanez (1, 2) , Sébastien Gallien (1, 4) , Christiane Copie (5, 6) , Mathieu Surénaud (2, 1) , Ayrin Kök (7) , Valerie Lorin (7) , Mathieu Fusaro (8) , Marie-Hélène Delfau-Larue (8) , Laurent Lefrou (9) , Thierry Prazuck (3) , Michael Levy (10) , Nabila Seddiki (1, 2) , Jean-Daniel Lelievre (4, 1, 2) , Hugo Mouquet (7, 1) , Yves Levy (1, 2, 4) , Sophie Huë (1, 8, 2)

1 VRI - Vaccine Research Institute [Créteil, France]
2 U955 Inserm - UPEC - IMRB - "From pathophysiology towards immune-basedinterventions in HIV infection" [Créteil]
3 Service des Maladies Infectieuses et Tropicales [CHR Orléans]
4 Service d'immunologie clinique et maladies infectieuses [Créteil]
5 Département de pathologie [Mondor]
6 IMRB - Institut Mondor de Recherche Biomédicale
7 Réponse humorale aux pathogènes
8 Laboratoire d'Immunologie Biologique [Créteil]
9 Service Hépato-gastro-entérologie et oncologie digestive [CHR Orléans]
10 Groupe Henri Mondor-Albert Chenevier

HIV-1 infection is associated with B cell dysregulation and dysfunction. In HIV-1-infected patients, we previously reported preservation of intestinal lymphoid structures and dendritic cell maturation pathways after early combination antiretroviral therapy (e-ART), started during the acute phase of the infection, compared with late combination antiretroviral therapy started during the chronic phase. In this study, we investigated whether the timing of combination antiretroviral therapy initiation was associated with the development of the HIV-1-specific humoral response in the gut. The results showed that e-ART was associated with higher frequencies of functional resting memory B cells in the gut. These frequencies correlated strongly with those of follicular Th cells in the gut. Importantly, frequencies of HIV-1 Env gp140-reactive B cells were higher in patients given e-ART, in whom gp140-reactive IgG production by mucosal B cells increased after stimulation. Moreover, IL-21 release by PBMCs stimulated with HIV-1 peptide pools was greater with e-ART than with late combination antiretroviral therapy. Thus, early treatment initiation helps to maintain HIV-1-reactive memory B cells in the gut as well as follicular Th cells, whose role is crucial in the development of potent affinity-matured and broadly neutralizing Abs.

Domaines: Sciences du Vivant [q-bio]

Cyril Planchais, Laurent Hocqueloux, Clara Ibanez, Sébastien Gallien, Christiane Copie, et al.. Early Antiretroviral Therapy Preserves Functional Follicular Helper T and HIV-Specific B Cells in the Gut Mucosa of HIV-1-Infected Individuals. Journal of Immunology, 2018, 200 (10), pp.3519-3529. ⟨10.4049/jimmunol.1701615⟩. ⟨pasteur-02634634⟩