IL-13 acutely augments HIV-specific and recall responses from HIV-1-infected subjects in vitro by modulating monocytes.
We show in this study that acute exposure of PBMCs derived from HIV-infected subjects to IL-13 results in increased recall T cell lymphoproliferative responses against HIV-1 p24 (n = 30, p < 0.0001) and other recall Ags (influenza, n = 43, p < 0.0001; purified protein derivative tuberculin, n = 6, p = 0.0299). This effect is due to a mechanism that acutely targets APC function in the adherent monocyte subset, as shown by the expansion of CD4(+) T cell responses following coculture of IL-13-treated enriched CD14(+) monocytes with donor-matched enriched CD4(+) T cells and Ag. Exposure to IL-13 over 18-72 h resulted in a significant enhancement of monocyte endocytosis (n = 11, p = 0.0005), CD86 expression (n = 12, p = 0.001), and a significant decrease in spontaneous apoptosis (n = 8, p = 0.008). Moreover, IL-13 exposure induced a significant decrease of significantly elevated constitutive levels of PBMC-secreted TNF-alpha (n = 14, p < 0.001) and IL-10 (n = 29, p < 0.001) within 18 h of exposure ex vivo, also reflected by decreased gene expression in the adherent cell population. Our data show that IL-13 is able to acutely enhance the function of the CD14(+) cell subset toward supporting Ag-specific cell-mediated responses in chronic HIV-1 infection.
Papasavvas
Emmanouil
E
The Wistar Institute, Philadelphia, PA 19104, USA.
Sun
Junwei
J
Luo
Qi
Q
Moore
Elizabeth C
EC
Thiel
Brian
B
MacGregor
Rob Roy
RR
Minty
Adrian
A
Mounzer
Karam
K
Kostman
Jay R
JR
Montaner
Luis J
LJ
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D017209:Apoptosis / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D004705:Endocytosis / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10