HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh) Subsets and Skewed B Cell Maturation.
Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+) individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined. Using a unique collection of splenocytes, we compared the frequency, phenotype and transcriptome of Tfh subsets in spleens from HIV negative (HIV-) and HIV+ subjects. We observed an increase of CXCR5+PD-1highCD57-Tfh and germinal center (GC) CD57+ Tfh in HIV+ spleens. Both subsets showed a reduced mRNA expression of the transcription factor STAT-3, co-stimulatory, regulatory and signal transduction molecules as compared to HIV- spleens. Similarly, Foxp3 expressing follicular regulatory T (Tfr) cells were increased, suggesting sustained GC reactions in chronically HIV+ spleens. As a consequence, GC B cell populations were expanded, however, complete maturation into memory B cells was reduced in HIV+ spleens where we evidenced a compromised production of B cell-activating cytokines such as IL-4 and IL-10. Collectively our data indicate that, although Tfh proliferation and GC reactions seem to be ongoing in HIV-infected spleens, Tfh "differentiation" and expression of costimulatory molecules is skewed with a profound effect on B cell maturation.
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.
Lucie
L
Colineau
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.
Angeline
A
Rouers
Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, United States of America.
Takuya
T
Yamamoto
The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
Yin
Y
Xu
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.
Alejandra
A
Urrutia
Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.
Hang-Phuong
HP
Pham
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.
Sylvain
S
Cardinaud
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.
Assia
A
Samri
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.
Karim
K
Dorgham
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.
Pierre-Grégoire
PG
Coulon
INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Rémi
R
Cheynier
INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Cochin, Paris, France.
Anne
A
Hosmalin
Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Département d'Immunologie Clinique, Hôpital Saint-Louis, Paris, France.
Eric
E
Oksenhendler
Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.
Adrien
A
Six
The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
Anthony D
AD
Kelleher
St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital, Sydney, Australia.
John
J
Zaunders
Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, United States of America.
Richard A
RA
Koup
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.
Brigitte
B
Autran
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.
Arnaud
A
Moris
Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.
Stéphanie
S
Graff-Dubois
D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D016207:Cytokines / Q000032:analysis; D004279:DNA, Viral / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000032:analysis; D013154:Spleen / Q000737:chemistry / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D016662:Virus Integration
D016207:Cytokines; D004279:DNA, Viral; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human