AUTHOR=Phetsouphanh Chansavath , Aldridge Daniel , Marchi Emanuele , Munier C. Mee Ling , Meyerowitz Jodi , Murray Lyle , Van Vuuren Cloete , Goedhals Dominique , Fidler Sarah , Kelleher Anthony , Klenerman Paul , Frater John 

TITLE=Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01844

DOI=10.3389/fimmu.2019.01844

ISSN=1664-3224

ABSTRACT=Cytotoxic CD4+ T cells play a prominent role in chronic viral infection. CD4+ CTL clones specific for HIV-1 Nef and Gag are capable of killing HIV-1 infected CD4+ T cells and macrophages. Additionally, HIV-specific cytolytic CD4+ T cell responses in acute HIV infection are predictive of disease progression. CD57 expression on CD4s identifies cytotoxic cells. These cells are dramatically increased in chronic HIV infection. CD57 expression correlates with cytolytic granules, granzyme B and perforin expression. They express lower CCR5 compared to CD57- cells, have less HIV total DNA, and are a minor component of the HIV reservoir. CD57+ CD4+ CTLs from EC are HIV-specific, can upregulate IFNγ with Gag peptide stimulation and maintain TbethighEomes+ transcription factor phenotype. This was not observed in viraemic controllers. The maintenance of HIV-specific CD4 cytotoxic function in Elite controllers together with CD8 CTL may be important for the control of HIV viraemia and of potential relevance to cure strategies.