Recall antigen activation induces prompt release of CCR5 ligands from PBMC: implication in memory responses and immunization.
CCR5 ligands RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta 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-1alpha and MIP-1beta, released in the course of memory responses may play a role in protecting CD4(+) memory T cells from infection.
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Room S613, Baltimore, MD 21201-1192, USA.
Lingling
L
Sun
Sayed F
SF
Abdelwahab
George K
GK
Lewis
Alfredo
A
Garzino-Demo
D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D019713:Receptors, CCR5 / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology*
D018925:Chemokines; D010446:Peptide Fragments; D019713:Receptors, CCR5; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C