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Journal of Virology, January 2009, p. 304-313, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01606-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

L. Buonaguro,1,2 M. L. Tornesello,1 R. C. Gallo,2 Franco M. Marincola,3 G. K. Lewis,2 and F. M. Buonaguro1*

Laboratory of Molecular Biology and Viral Oncogenesis & AIDS Reference Center, Istituto Nazionale Tumori Fond. G. Pascale, Naples, Italy,1 Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland,2 Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland3

Received 29 July 2008/ Accepted 10 October 2008

We have recently shown that human immunodeficiency virus type 1 (HIV-1) Pr55gag 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.

* Corresponding author. Mailing address: Laboratory of Molecular Biology and Viral Oncogenesis & AIDS Reference Center, Istituto Nazionale Tumori Fond. G. Pascale, Via Mariano Semmola, 1, 80131 Naples, Italy. Phone: 39-81-5903.830. Fax: 39-081-5451276. E-mail: irccsvir{at}unina.it

{triangledown} Published ahead of print on 22 October 2008.

Journal of Virology, January 2009, p. 304-313, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01606-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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