Enhanced HIV expression during Th2-oriented responses explained by the opposite regulatory effect of IL-4 and IFN-gamma of fusin/CXCR4.
The human alpha-chemokine receptor fusin/CXCR4 is an important cofactor for entry of T lymphocyte-tropic HIV-1 strains. We investigated the possible regulatory role of T cell cytokine patterns on CXCR4 as well as HIV expression by using in vitro models of both secondary and primary immune responses. Antigen-specific memory CD4+ T cells infected with a T-tropic HIV-1 strain showed significantly higher CXCR4 and HIV-1 expression in Th0/2-oriented responses in comparison with Th1-oriented responses. Similarly, in naive CD4+ T cells activated in the presence of IL-4 or IL-12 and infected with the same T-tropic strain, IL-4 up-regulated whereas IL-12 down-regulated both CXCR4 and HIV-1 expression. The down-regulatory effect of IL-12 on CXCR4 expression was found to be dependent on its capacity to induce IFN-gamma production. These observations can account for the higher risk of progression in HIV-1-infected individuals undergoing Th0/2-oriented immune responses.
Galli
G
G
Institute of Internal Medicine and Immunoallergology, University of Florence, Italy.
Annunziato
F
F
Mavilia
C
C
Romagnani
P
P
Cosmi
L
L
Manetti
R
R
Pupilli
C
C
Maggi
E
E
Romagnani
S
S
D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology* / Q000821:virology; D015854:Up-Regulation / Q000276:immunology
D016655:HIV Core Protein p24; D019718:Receptors, CXCR4; D015847:Interleukin-4; D007371:Interferon-gamma