Th2 Polarization in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus (HIV)-Infected Subjects, as Activated by HIV Virus-Like Particles

Abstract

We have recently shown that human immunodeficiency virus type 1 (HIV-1) Pr55 gag virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A, induce maturation and activation of monocyte-derived dendritic cells (MDDCs) with a production of Th1-and Th2-specific cytokines. Furthermore, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4 ؉ T cells in an ex vivo immunization assay. In the present study, we show that similar data can be obtained directly with fresh peripheral blood mononuclear cells (PBMCs), and the HIV-1 seropositivity status, with either low or high viremia, does not significantly impair the immune activation status and the responsiveness of circulating monocyte CD14؉ cell populations to an immunogenic stimulus. Some HIV-1-seropositive subjects, however, show a complete lack of maturation induced by HIV-VLPs in CD14؉ circulating cells, which does not consistently correlate with an advanced status of HIV-1 infection. The established Th2 polarization in both HIV-seropositive groups is efficiently boosted by HIV-VLP induction and does not switch into a Th1 pattern, strongly suggesting that specific Th1 adjuvants would be required for therapeutic effectiveness in HIV-1-infected subjects. These results indicate the possibility of screening PBMCs for donor susceptibility to an immunogen treatment, which would greatly simplify the identification of "responsive" vaccinees as well as the understanding of eventual failures in individuals enrolled in clinical trials.

Altered Host-Microbe Interaction in HIV: A Target for Intervention with Pro- and Prebiotics

“…Recently, it was suggested that the induction of T helper-2 (Th-2) cytokine synthesis [65,66] and the gradual increase of IL-4 and IgE [67,68] observed after HIV infection, might be due to a Th-2 response to viral proteins, such as gp-120, p24, and p17 [69]. It is well known that HIV patients suffer from high rates of allergies [70] and the ability of subgroups of HIV patients to maintain a vigorous Th-1 response and higher levels of IFN-γ is associated with increased survival [71,72].…”

Expresión diferencial en placenta de beta-defensinas humanas y detección de variantes alélicas en el gen DEFB1 de madres positivas para VIH-1

“…Furthermore, the TH2 cytokines IL-4, IL-10, and IL-13 have shown to down-regulate the HBD-3 expression on keratinocytes (64), but are upregulated during pregnancy (65) and are also induced by HIV-1 (66,67). Therefore, HIV-1 may induce an over-expression of this cytokine profile, thereby decreasing the levels of HBD-3 in placenta tissue of seropositive mothers.…”

HIV-1 Gag-Virus-Like Particles Induce Natural Killer Cell Immune Responses via Activation and Maturation of Dendritic Cells

“…The results from phase III trials showed that purified recombinant Env-gp120 failed to protect against HIV-1 infection and also failed to induce production of neutralizing antibodies to diverse primary isolates. The presence of HIV-1 Env-gp120 in GagVLPs switches the Th2 polarization in peripheral blood mononuclear cells from HIV-infected subjects [34][35][36] . For these reasons, HIV-1 Gag-VLPs are preferred as an HIV-1 vaccine candidate.…”