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Scientific Fields
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Published in Nature communications - 26 Jan 2022

Claireaux M, Robinot R, Kervevan J, Patgaonkar M, Staropoli I, Brelot A, Nouël A, Gellenoncourt S, Tang X, Héry M, Volant S, Perthame E, Avettand-Fenoël V, Buchrieser J, Cokelaer T, Bouchier C, Ma L, Boufassa F, Hendou S, Libri V, Hasan M, Zucman D, de Truchis P, Schwartz O, Lambotte O, Chakrabarti LA,

Link to Pubmed [PMID] – 35082297

Link to DOI – 10.1038/s41467-022-28130-0

Nat Commun 2022 Jan; 13(1): 521

HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control.

https://pubmed.ncbi.nlm.nih.gov/35082297