Experimental infection of a nonhuman primate with Loa loa induces transient strong immune activation followed by peripheral unresponsiveness of helper T cells.
Human infection with the parasite Loa loa is characterized by a good adaptation between the parasite and its host. One portion of the human population harbors only adult worms in subcutaneous tissues, whereas another portion also harbors the L1 microfilarial stage in peripheral circulation. This study was undertaken to understand the mechanisms by which the parasite evades or modulates host immunological attack. The cellular responses, based on T-cell proliferation, to the production of various cytokines (interleukin-2 [IL-2], gamma interferon [IFN-gamma], IL-4, and IL-5) and to expression of cytokine (IL-2, IFN-gamma, IL-4, IL-5, IL-10, and IL-12) mRNAs were investigated during the experimental infection with human parasite L. loa of a nonhuman primate which has been shown to display a spectrum of disease similar to that found in humans. Our results indicate that a T-cell unresponsiveness occurs when female worm products are released into the peripheral circulation, preceded by a transient period of strong T-cell proliferation, cytokine production, and cytokine mRNA expression. In the unresponsive state, only IL-10 mRNA is expressed, suggesting a role for IL-10 in down-regulation and maintenance of unresponsiveness. Taken together, these results indicate that both IL-10 production, which is known to inhibit B7 expression on monocytes, and the massive release of female products in the blood where T cells encounter antigens presented by nonactivated B lymphocytes, which lack costimulatory signals, should contribute to the inactivation of T cells.
Leroy
E
E
Centre International de Recherches Medicales de Franceville, Gabon. eleroy@cauchy.cirmfrv.fr
Baize
S
S
Wahl
G
G
Egwang
T G
TG
Georges
A J
AJ
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology / Q000494:pharmacology; D002455:Cell Division; D015536:Down-Regulation / Q000276:immunology; D004587:Electrophoresis, Agar Gel; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008118:Loiasis / Q000097:blood / Q000276:immunology*; D010215:Papio; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000947:Antigens, Helminth; D007378:Interleukins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma