PMID- 28463977
OWN - NLM
STAT- MEDLINE
DCOM- 20170905
LR  - 20190208
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - Production of IgG antibodies to pneumococcal polysaccharides is associated with 
      expansion of ICOS+ circulating memory T follicular-helper cells which is impaired 
      by HIV infection.
PG  - e0176641
LID - 10.1371/journal.pone.0176641 [doi]
LID - e0176641
AB  - Dysfunction of T follicular-helper (TFH) cells is a possible cause of impaired 
      germinal centre (GC) and IgG antibody responses in individuals with human 
      immunodeficiency virus-1 (HIV-1) infection and might contribute to decreased 
      magnitude and isotype diversification of IgG antibodies to pneumococcal 
      polysaccharides (PcPs). We examined the production of IgG1 and IgG2 antibodies to 
      PcPs 4, 6B, 9V and 14 by enumerating antibody secreting cells (ASCs) at day (D) 7 
      and determining fold-increase in serum antibody levels at D28 after vaccination 
      with unconjugated PcPs in HIV seronegative subjects (n = 20) and in HIV patients 
      who were receiving antiretroviral therapy (ART) (n = 28) or who were ART-naive (n 
      = 11) and determined their association with ICOS+ and ICOS- circulating memory 
      TFH (cmTFH) cells (CD4+CD45RA-CD27+CXCR5+PD-1+) and short lived plasmablasts 
      (SPBs) at D7, and with PcP-specific and total IgM+ and IgG+ memory B cells at D0. 
      In HIV seronegative subjects, production of IgG1+ and IgG2+ ASCs was consistently 
      associated with the frequency of ICOS+ cmTFH cells but not ICOS- cmTFH cells or 
      memory B cells. In contrast, post-vaccination ASCs in HIV patients, regardless of 
      ART status, were lower than in HIV seronegative subjects and not associated with 
      ICOS+ cmTFH cells, the expansion of which was absent (ART-naive patients) or much 
      lower than in HIV seronegative subjects (ART-treated patients). Production of 
      SPBs was also lower in ART-naive patients. Fold-increase in IgG2 antibodies at 
      D28 also correlated with ICOS+ cmTFH cells at D7 in HIV seronegative subjects but 
      not in HIV patients. These novel findings provide evidence that ICOS+ cmTFH cells 
      contribute to the regulation of PcP-specific IgG antibody responses, including 
      isotype diversification, and that TFH cell dysfunction may be a cause of impaired 
      PcP-specific IgG antibody responses and increased susceptibility to pneumococcal 
      disease in HIV patients.
FAU - Abudulai, Laila N
AU  - Abudulai LN
AD  - School of Pathology & Laboratory Medicine, The University of Western Australia, 
      Perth, Australia.
FAU - Fernandez, Sonia
AU  - Fernandez S
AUID- ORCID: 0000-0001-8753-466X
AD  - School of Pathology & Laboratory Medicine, The University of Western Australia, 
      Perth, Australia.
FAU - Corscadden, Karli
AU  - Corscadden K
AD  - Center for Vaccine and Infectious Disease Research, Telethon Kids Institute, The 
      University of Western Australia, Perth, Australia.
FAU - Burrows, Sally A
AU  - Burrows SA
AUID- ORCID: 0000-0002-8499-4537
AD  - School of Medicine & Pharmacology, The University of Western Australia, Perth, 
      Australia.
FAU - Hunter, Michael
AU  - Hunter M
AD  - Department of Infectious Diseases, Prince of Wales Hospital, Sydney, Australia.
AD  - Prince of Wales Clinical School, University of New South Wales, Sydney, 
      Australia.
FAU - Tjiam, M Christian
AU  - Tjiam MC
AD  - School of Pathology & Laboratory Medicine, The University of Western Australia, 
      Perth, Australia.
FAU - Kirkham, Lea-Ann S
AU  - Kirkham LS
AD  - Center for Vaccine and Infectious Disease Research, Telethon Kids Institute, The 
      University of Western Australia, Perth, Australia.
AD  - School of Paediatrics and Child Health, The University of Western Australia, 
      Perth, Australia.
FAU - Post, Jeffrey J
AU  - Post JJ
AD  - Department of Infectious Diseases, Prince of Wales Hospital, Sydney, Australia.
AD  - Prince of Wales Clinical School, University of New South Wales, Sydney, 
      Australia.
FAU - French, Martyn A
AU  - French MA
AD  - School of Pathology & Laboratory Medicine, The University of Western Australia, 
      Perth, Australia.
AD  - Department of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory 
      Medicine, Perth, Australia.
LA  - eng
PT  - Journal Article
DEP - 20170502
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-HIV Agents)
RN  - 0 (ICOS protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Inducible T-Cell Co-Stimulator Protein)
RN  - 0 (Pneumococcal Vaccines)
RN  - 0 (Polysaccharides, Bacterial)
SB  - IM
MH  - Anti-HIV Agents/therapeutic use
MH  - Antibody Formation/immunology
MH  - HIV Infections/drug therapy/*immunology
MH  - Humans
MH  - Immunoglobulin G/*immunology
MH  - Inducible T-Cell Co-Stimulator Protein/*immunology
MH  - Pneumococcal Infections/*immunology
MH  - Pneumococcal Vaccines/immunology
MH  - Polysaccharides, Bacterial/*immunology
MH  - T-Lymphocytes, Helper-Inducer/immunology
PMC - PMC5413043
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/05/04 06:00
MHDA- 2017/09/07 06:00
PMCR- 2017/05/02
CRDT- 2017/05/03 06:00
PHST- 2017/03/29 00:00 [received]
PHST- 2017/04/13 00:00 [accepted]
PHST- 2017/05/03 06:00 [entrez]
PHST- 2017/05/04 06:00 [pubmed]
PHST- 2017/09/07 06:00 [medline]
PHST- 2017/05/02 00:00 [pmc-release]
AID - PONE-D-17-10373 [pii]
AID - 10.1371/journal.pone.0176641 [doi]
PST - epublish
SO  - PLoS One. 2017 May 2;12(5):e0176641. doi: 10.1371/journal.pone.0176641. 
      eCollection 2017.