Antigen stimulation induces HIV envelope gp120-specific CD4(+) T cells to secrete CCR5 ligands and suppress HIV infection.
CD4(+) T cells are critical for effective immune responses against HIV, but they are also the main cell type targeted by the virus. To investigate the key factors that could protect these cells from infection, we evaluated the capacity of HIV gp120-specific human CD4(+) T cells to produce chemokines that inhibit HIV and determined their contribution in suppressing infection in the cells. Antigen stimulation of the CD4(+) T cells elicited production of high amounts of CCR5 chemokines MIP-1alpha (CCL3), MIP-1beta (CCL4), and RANTES (CCL5). Production of these CCR5 ligands was more readily and reproducibly detected than that of IFN-gamma or IL-2. Importantly, in association with secretion of the CCR5 ligands, antigen stimulation made these CD4(+) T cells more resistant to CCR5-tropic HIV-1. Conversely, in the absence of antigen stimulation, the cells were readily infected by the virus, and after infection, their capacity to produce MIP-1beta and IFN-gamma rapidly declined. Thus, vaccines that trigger HIV-specific CD4(+) T cells to elicit robust and rapid production of anti-viral chemokines would be advantageous. Such responses would protect virus-specific CD4(+) T cells from HIV infection and preserve their critical functions in mounting and maintaining long-lasting immunity against the virus.
Kaur
Gurvinder
G
Department of Veterans Affairs New York Harbor Healthcare System and Department of Pathology, New York University School of Medicine, New York, NY, USA.
Tuen
Michael
M
Virland
Diana
D
Cohen
Sandra
S
Mehra
Narinder K
NK
Münz
Christian
C
Abdelwahab
Sayed
S
Garzino-Demo
Alfredo
A
Hioe
Catarina E
CE
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000096:biosynthesis / Q000276:immunology; D054407:Chemokine CCL4 / Q000096:biosynthesis / Q000276:immunology; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D019713:Receptors, CCR5 / Q000276:immunology*
C515429:CCL3 protein, human; C066507:CCL4 protein, human; C483024:CCL5 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; C514793:gp120 protein, Human immunodeficiency virus 1