Immune Netw.  2005 Jun;5(2):68-77. 10.4110/in.2005.5.2.68.

Opposite Roles of B7.1 and CD28 Costimulatory Molecules for Protective Immunity against HSV-2 Challenge in a gD DNA Vaccine Model

• Weiner DB
• Sin JI

• KMID: 2150600
• DOI: http://doi.org/10.4110/in.2005.5.2.68

Abstract

BACKGROUND
Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. METHODS: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. RESULTS: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. CONCLUSION: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

Keyword

Costimulatory molecules; cytokines; chemokines; infectious immunity-virus; Th1/Th2

MeSH Terms

Animals
Antibodies
Antibody Formation
Antigen Presentation
Bias (Epidemiology)
Cell Proliferation
Chemokines
Cytokines
DNA*
DNA, Complementary
Enzyme-Linked Immunosorbent Assay
Herpesvirus 2, Human*
Immunity, Cellular
Immunoglobulin G
Mice
Survival Rate
Thymidine
Antibodies
Chemokines
Cytokines
DNA
DNA, Complementary
Immunoglobulin G
Thymidine