Altered cytokine production and accessory cell function after HIV-1 infection.
We investigated cytokine production and accessory cell function in human macrophage hybridoma cell lines and primary monocytes after infection with HIV-1. HIV-1 infection induced IL-10 production in the macrophage hybridoma cell line with loss of IL-12 1 wk after infection. There were also significant increases in production of IL-10 (537 +/- 521 vs 687 +/- 625 pg/ml) while there was a reduction in IL-12 (6.3 +/- 3.1 vs 1.2 +/- 1.0 pg/ml, p = 0.021) in the primary monocytes 5 days after HIV-1 infection. In addition, the hybridoma cell lines and primary monocytes failed to support PHA, Con A, PWM, or anti-CD3- induced T cell proliferation 1 wk after infection. The viability of the T cells cocultured with the HIV-1-infected macrophage cell lines or the primary monocytes as determined by propidium iodide staining was unaltered and there was no increase in apoptosis-specific DNA strand breaks or increased expression of Bcl-2 in the T cells. No soluble suppressor factor was present, since UV-inactivated supernatants from the hybridoma cell line and primary monocytes failed to inhibit mitogen- and anti-CD3-induced T cell proliferation. Early events in T cell activation, including calcium flux and phosphotyrosine kinase activity, were intact in the T cells cocultured with the HIV-1- infected hybridomas and monocytes but there was reduced IL-2 production. Addition of exogenous IL-2 restored the proliferative responses. Taken together, these data suggest that alteration of cytokine production and accessory cell function for mitogens and anti-CD3-induced T cell proliferation independent of induction of apoptosis, suppressor factor production, or inhibition of T cell signaling occurs very early after HIV-1 infection and may contribute to the global immunosuppression observed in AIDS.
Yoo
J
J
Division of Clinical Immunology, Mount Sinai Medical Center, New York, NY 10029, USA.
Chen
H
H
Kraus
T
T
Hirsch
D
D
Polyak
S
S
George
I
I
Sperber
K
K
D017209:Apoptosis; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology* / Q000821:virology
D017252:CD3 Complex; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016753:Interleukin-10; D018664:Interleukin-12