TY - JOUR
T1 - Early initiation of antiretroviral treatment postSIV infection does not resolve lymphoid tissue activation
AU - Hong, Jung J.
AU - Di Volpe Silveira, Eduardo L.
AU - Amancha, Praveen K.
AU - Byrareddy, Siddappa N.
AU - Gumber, Sanjeev
AU - Chang, Kyu Tae
AU - Ansari, Aftab A.
AU - Villinger, Francois
N1 - Funding Information:
The work was supported in part by NIH grants R01 AI078775 and 8R24OD010947 to F.V., NIH grant R01 AI098628 to A.A.A., NIH OD-51OD11132 to the Yerkes NPRC.
PY - 2017/8/24
Y1 - 2017/8/24
N2 - Objective: Germinal center resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV) replication. But the dynamics of germinal centers upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post-SIV infection are not fully understood. Design: Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART initiation. These tissues and cells were analyzed for frequencies of TFH cells and assignment of germinal center scores. Results: Modest but significant increases in TFH cells and hyperplastic follicles with large germinal centers were noted during the acute phase of SIV infection (week 5/pre-ART). However, 6 weeks after ART initiation, substantial increases in germinal center TFH cells, germinal center B cells, hyperplastic follicles with large germinal centers, and abundant local IL-21 production were observed, whereas levels of SIV RNA and DNA of lymph nodes had decreased to barely detectable values along with barely detectable levels of SIV antibody-producing cells. An additional 6 weeks of ART did not appreciably decrease germinal center TFH or germinal center scores. Conclusion: Thus, although early ART rapidly controls SIV replication, it does not regulate early lymphoid activation, which may contribute to the seeding and magnitude of viral reservoirs.
AB - Objective: Germinal center resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV) replication. But the dynamics of germinal centers upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post-SIV infection are not fully understood. Design: Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART initiation. These tissues and cells were analyzed for frequencies of TFH cells and assignment of germinal center scores. Results: Modest but significant increases in TFH cells and hyperplastic follicles with large germinal centers were noted during the acute phase of SIV infection (week 5/pre-ART). However, 6 weeks after ART initiation, substantial increases in germinal center TFH cells, germinal center B cells, hyperplastic follicles with large germinal centers, and abundant local IL-21 production were observed, whereas levels of SIV RNA and DNA of lymph nodes had decreased to barely detectable values along with barely detectable levels of SIV antibody-producing cells. An additional 6 weeks of ART did not appreciably decrease germinal center TFH or germinal center scores. Conclusion: Thus, although early ART rapidly controls SIV replication, it does not regulate early lymphoid activation, which may contribute to the seeding and magnitude of viral reservoirs.
KW - antiretroviral drugs
KW - follicular helper T cell
KW - germinal center
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U2 - 10.1097/QAD.0000000000001576
DO - 10.1097/QAD.0000000000001576
M3 - Article
C2 - 28692537
AN - SCOPUS:85021978111
VL - 31
SP - 1819
EP - 1824
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 13
ER -