TY - JOUR
T1 - Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples
T2 - Humoral Response Potentially Implicated in Modulating Transmission Rates
AU - Ruiz, María Julia
AU - Salido, Jimena
AU - Abusamra, Lorena
AU - Ghiglione, Yanina
AU - Cevallos, Cintia
AU - Damilano, Gabriel
AU - Rodriguez, Ana María
AU - Trifone, César
AU - Laufer, Natalia
AU - Giavedoni, Luis D.
AU - Sued, Omar
AU - Salomón, Horacio
AU - Gherardi, María Magdalena
AU - Turk, Gabriela
N1 - Funding Information:
This work was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica and GlaxoSmithKline (PICT2012, Grant # 0475 and PICTO-GSK, Grant # 2013/0006 ) and from Universidad de Buenos Aires (UBACyT 2013–2016, Grant # 20020120200263BA ) to GT. This investigation also used resources that were supported by the Southwest National Primate Research Center grant P51 OD011133 from the Office of Research Infrastructure Programs , National Institutes of Health (NIH) to LDG. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Funding Information:
This work was supported by grants from the Agencia Nacional de Promoci?n Cient?fica y Tecnol?gica and GlaxoSmithKline (PICT2012, Grant # 0475 and PICTO-GSK, Grant # 2013/0006) and from Universidad de Buenos Aires (UBACyT 2013?2016, Grant # 20020120200263BA) to GT. This investigation also used resources that were supported by the Southwest National Primate Research Center grant P51 OD011133 from the Office of Research Infrastructure Programs, National Institutes of Health (NIH) to LDG. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
PY - 2017/12
Y1 - 2017/12
N2 - As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV+-P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV− donors (HD). Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.
AB - As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV+-P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV− donors (HD). Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.
KW - ADCC
KW - HIV-1
KW - HIV-1 transmission
KW - Serodiscordant couples
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U2 - 10.1016/j.ebiom.2017.11.001
DO - 10.1016/j.ebiom.2017.11.001
M3 - Article
C2 - 29129698
AN - SCOPUS:85033361672
VL - 26
SP - 25
EP - 37
JO - EBioMedicine
JF - EBioMedicine
SN - 2352-3964
ER -