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International Immunology Advance Access originally published online on October 4, 2004
International Immunology 2004 16(11):1623-1631; doi:10.1093/intimm/dxh164
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© 2004 The Japanese Society for Immunology

Recall antigen activation induces prompt release of CCR5 ligands from PBMC: implication in memory responses and immunization

Lingling Sun, Sayed F. Abdelwahab1, George K. Lewis and Alfredo Garzino-Demo

Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Room S613, Baltimore, MD 21201-1192, USA
1 Present address: Department of Microbiology and Immunology, El-minia Faculty of Medicine, El-minia University, El-minia 61111, Egypt

Correspondence to: A. Garzino-Demo; E-mail: garzinod{at}umbi.umd.edu

CCR5 ligands RANTES, macrophage inflammatory protein (MIP)-1{alpha} and MIP-1ß are potent and specific inhibitors of strains of human immunodeficiency virus (HIV) that use CCR5 as a receptor, which are the strains most involved in primary infection. Recently, we observed that release of CCR5 ligands is a consistent and reproducible parameter of response to antigen activation in studies using PBMC. In this study, we show that CCR5 ligands are released upon antigen [Fragment C of tetanus toxin (TTC)] stimulation in 81% (n = 16) of subjects tested, as detected by a standard ELISA in tissue culture supernatants of antigen-activated cells. In contrast, ELISA for other cytokines from the same supernatants revealed that IFN-{gamma} release could be detected only in 31% of subjects, IL-2 could be detected only in 12% of the subjects and IL-4 was not detectable in any of the subjects tested. Similarly, proliferative responses to TTC, as measured by a standard tritiated thymidine incorporation assay, were detectable in only 56% of the subjects. Similar observations have been reported in flow cytometric studies, and resonate with previous findings emphasizing the role of CCR5 in T cell responses. In addition, the levels of CCR5 ligands in supernatants from antigen-activated cells were sufficient to inhibit infection of R5 HIV. Thus, CCR5 ligands might play a role in controlling HIV in vivo. Taken together, these observations suggest that CCR5 ligands, and in particular MIP-1{alpha} and MIP-1ß, released in the course of memory responses may play a role in protecting CD4+ memory T cells from infection.

Keywords: chemokines, lymphoproliferation, MIP-1{alpha}, MIP-1ß, RANTES

Transmitting editor: G. Trinchieri


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