LFA-3 plasmid DNA enhances Ag-specific humoral- and cellular-mediated protective immunity against herpes simplex virus-2 in vivo: involvement of CD4+ T cells in protection.
Adhesion molecules are important for cell trafficking and delivery of secondary signals for stimulation of T cells and antigen-presenting cells (APCs) in a variety of immune and inflammatory responses. Adhesion molecules lymphocyte function-associated antigen (LFA)-1 and CD2 on T cells recognize intercellular adhesion molecule (ICAM)-1 and LFA-3 on APCs, respectively. Recent studies have suggested that these molecules might play a regulatory role in antigen-specific immune responses. To investigate specific roles of adhesion molecules in immune induction we coimmunized LFA-3 and ICAM-1 cDNAs with a gD plasmid vaccine and then analyzed immune modulatory effects and protection against lethal herpes simplex virus (HSV)-2 challenge. We observed that gD-specific IgG production was enhanced by LFA-3 coinjection. However, little change in IgG production was observed by ICAM-1 coinjection. Furthermore, both Th1 and Th2 IgG isotype production was driven by LFA-3. LFA-3 also enhanced Th cell proliferative responses and production of interleukin (IL)-2, interferon-gamma, IL-4, and IL-10 from splenocytes. In contrast, ICAM-1 showed slightly increasing effects on T-cell proliferation responses and cytokine production. beta-Chemokine production (RANTES, MIP-1alpha, and MCP-1) was also influenced by LFA-3 or ICAM-1. When animals were challenged with a lethal dose of HSV-2, LFA-3-coimmunized animals exhibited an enhanced survival rate, as compared to animals given ICAM-1 or gD DNA vaccine alone. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vitro and in vivo T-cell subset deletion. These studies demonstrate that adhesion molecule LFA-3 can play an important role in generating protective antigen-specific immunity in the HSV model system through increased induction of CD4+ Th1 T-cell subset.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 505 Stellar-Chance Lab, 422 Curie Drive, Philadelphia, Pennsylvania 19104, USA.
J I
JI
Sin
J
J
Kim
K
K
Dang
D
D
Lee
C
C
Pachuk
C
C
Satishchandran
D B
DB
Weiner
C
C
Patchuk
D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018968:CD58 Antigens / Q000276:immunology / Q000627:therapeutic use*; D019742:Chemokines, CC / Q000096:biosynthesis; D005260:Female; D006558:Herpes Genitalis / Q000401:mortality / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use; D014621:Vagina / Q000276:immunology; D014765:Viral Vaccines / Q000627:therapeutic use*
D018968:CD58 Antigens; D019742:Chemokines, CC; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007378:Interleukins; D019444:Vaccines, DNA; D014765:Viral Vaccines; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma