TY - JOUR
T1 - Regulatory and helper follicular T cells and antibody avidity to simian immunodeficiency virus glycoprotein 120
AU - Blackburn, Matthew J.
AU - Zhong-Min, Ma
AU - Caccuri, Francesca
AU - McKinnon, Katherine
AU - Schifanella, Luca
AU - Guan, Yongjun
AU - Gorini, Giacomo
AU - Venzon, David
AU - Fenizia, Claudio
AU - Binello, Nicolò
AU - Gordon, Shari N.
AU - Miller, Chris J
AU - Franchini, Genoveffa
AU - Vaccari, Monica
PY - 2015/10/1
Y1 - 2015/10/1
N2 - T follicular regulatory cells (TFR) are a suppressive CD4+ T cell subset that migrates to germinal centers (GC) during Ag presentation by upregulating the chemokine receptor CXCR5. In the GC, TFR control T follicular helper cell (TFH) expansion andmodulate the development of high-affinity Ag-specific responses. In this study, we identified and characterized TFR as CXCR5+CCR7- "follicular" T regulatory cells in lymphoid tissues of healthy rhesus macaques, and we studied their dynamics throughout infection in a welldefined animal model of HIV pathogenesis. TFR were infected by SIVmac251 and had comparable levels of SIV DNA to CXCR5-CCR7+ "T zone" T regulatory cells and TFH. Contrary to the SIV-associated TFH expansion in the chronic phase of infection, we observed an apparent reduction of TFR frequency in cell suspension, as well as a decrease of CD3+Foxp3+ cells in the GC of intact lymph nodes. TFR frequency was inversely associated with the percentage of TFH and, interestingly, with the avidity of the Abs that recognize the SIV gp120 envelope protein. Our findings show changes in the TFH/TFR ratio during chronic infection and suggest possible mechanisms for the unchecked expansion of TFH cells in HIV/SIV infection.
AB - T follicular regulatory cells (TFR) are a suppressive CD4+ T cell subset that migrates to germinal centers (GC) during Ag presentation by upregulating the chemokine receptor CXCR5. In the GC, TFR control T follicular helper cell (TFH) expansion andmodulate the development of high-affinity Ag-specific responses. In this study, we identified and characterized TFR as CXCR5+CCR7- "follicular" T regulatory cells in lymphoid tissues of healthy rhesus macaques, and we studied their dynamics throughout infection in a welldefined animal model of HIV pathogenesis. TFR were infected by SIVmac251 and had comparable levels of SIV DNA to CXCR5-CCR7+ "T zone" T regulatory cells and TFH. Contrary to the SIV-associated TFH expansion in the chronic phase of infection, we observed an apparent reduction of TFR frequency in cell suspension, as well as a decrease of CD3+Foxp3+ cells in the GC of intact lymph nodes. TFR frequency was inversely associated with the percentage of TFH and, interestingly, with the avidity of the Abs that recognize the SIV gp120 envelope protein. Our findings show changes in the TFH/TFR ratio during chronic infection and suggest possible mechanisms for the unchecked expansion of TFH cells in HIV/SIV infection.
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U2 - 10.4049/jimmunol.1402699
DO - 10.4049/jimmunol.1402699
M3 - Article
C2 - 26297759
AN - SCOPUS:84942475241
VL - 195
SP - 3227
EP - 3236
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -