AIDS progression is associated with the emergence of IL-17-producing cells early after simian immunodeficiency virus infection.
IL-17 is a potent effector cytokine involved in inflammatory response and antimicrobial defense. We report that SIV infection of rhesus macaques (RMs) results in the emergence of IL-17-expressing cells during the acute phase. This subpopulation appears at day 14 postinfection concomitantly with an increase in TGF-beta and IL-18 expression. This subset, which exhibits phenotypic markers of NK T cells (NKT), rather than Th17 CD4 cells, persists during the chronic phase and is higher in noncontrollers SIV-infected RMs compared with controllers SIV-infected RMs. In contrast, in the nonpathogenic model of SIVagm infection of African green monkeys, no change in the level of IL-17-expressing cells is observed in lymphoid organs. Consistent with the emergence of TGF-beta and IL-18 during the acute phase in SIV-infected RMs, but not in SIV-infected African green monkeys, we demonstrate that in vitro TGF-beta and IL-18 induce the differentiation and expansion of IL-17+NKT+. Altogether, these results demonstrate that IL-17-producing NKT are associated with the pathogenesis of SIV in RMs and suggest that TGF-beta and IL-18 play a role in their development.
Campillo-Gimenez
Laure
L
Institut National de la Santé et de la Recherche Médicale (U 955), Faculté de Médecine de Créteil, Hôpital Henri Mondor, Créteil, France.
Cumont
Marie-Christine
MC
Fay
Michèle
M
Kared
Hassen
H
Monceaux
Valérie
V
Diop
Ousmane
O
Müller-Trutwin
Michaela
M
Hurtrel
Bruno
B
Lévy
Yves
Y
Zaunders
John
J
Dy
Michel
M
Leite-de-Moraes
Maria C
MC
Elbim
Carole
C
Estaquier
Jérôme
J
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D018450:Disease Progression; D016130:Immunophenotyping; D020381:Interleukin-17; D020382:Interleukin-18 / Q000096:biosynthesis / Q000502:physiology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology* / Q000821:virology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology
D020381:Interleukin-17; D020382:Interleukin-18; D016212:Transforming Growth Factor beta