Critical contribution of CD28-CD80/CD86 costimulatory pathway to protection from Trypanosoma cruzi infection.

Abstract

The CD28-CD80/CD86-mediated T-cell costimulatory pathway has been variably implicated in infectious immunity. In this study, we investigated the role of this costimulatory pathway in resistance to Trypanosoma cruzi infection by using CD28-deficient mice and blocking antibodies against CD80 and CD86. CD28-deficient mice exhibited markedly exacerbated T. cruzi infection, as evidenced by unrelenting parasitemia and 100% mortality after infection with doses that are nonlethal in wild-type mice. The blockade of both CD80 and CD86 by administering specific monoclonal antibodies also exacerbated T. cruzi infection in wild-type mice. Splenocytes from T. cruzi-infected, CD28-deficient mice exhibited greatly impaired gamma interferon production in response to T. cruzi antigen stimulation in vitro compared to those from infected wild-type mice. The induction of T. cruzi antigen-specific CD8(+) T cells was also impaired in T. cruzi-infected, CD28-deficient mice. In addition to these defects in natural protection against T. cruzi infection, CD28-deficient mice were also defective in the induction of CD8(+)-T-cell-mediated protective immunity against T. cruzi infection by DNA vaccination. These results demonstrate, for the first time, a critical contribution of the CD28-CD80/CD86 costimulatory pathway not only to natural protection against primary T. cruzi infection but also to DNA vaccine-induced protective immunity to Chagas' disease.

• Authors: Yasushi Miyahira, Masaharu Katae, Seiki Kobayashi, Tsutomu Takeuchi, Yoshinosuke Fukuchi, Ryo Abe, Ko Okumura, Hideo Yagita, Takashi Aoki
• Journal: Infection and immunity (Infect Immun) Vol. 71 Issue 6 Pg. 3131-7 (Jun 2003) ISSN: 0019-9567 [Print] United States
• PMID: 12761091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• B7-1 Antigen
• B7-2 Antigen
• CD28 Antigens
• Cd86 protein, mouse
• Membrane Glycoproteins
• Protozoan Vaccines
• Vaccines, DNA
• Interferon-gamma

Topics

• Animals
• Antigens, CD (physiology)
• B7-1 Antigen (physiology)
• B7-2 Antigen
• CD28 Antigens (physiology)
• Disease Susceptibility
• Female
• Interferon-gamma (biosynthesis)
• Membrane Glycoproteins (physiology)
• Mice
• Mice, Inbred BALB C
• Protozoan Vaccines (immunology)
• Spleen (cytology)
• Trypanosoma cruzi (immunology)
• Vaccines, DNA (immunology)