Inhibitory effects of CTLA4-Ig fusion protein on the proliferation of T cell and the antibody production of B cell.
- Author:
Seong Ok JANG
1
;
So Yeon LEE
;
Soo Jong HONG
Author Information
1. Asan Institute for Life Sciences, Seoul, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
CTLA4-Ig;
costimulation;
T cell;
B cell;
anergy
- MeSH:
Abatacept;
Animals;
Antibody Formation*;
Asthma;
Cell Proliferation;
CHO Cells;
Cricetinae;
Humans;
Lymphocyte Subsets;
Lymphocytes;
Models, Animal;
Mucous Membrane;
T-Lymphocytes;
Transfection
- From:Journal of Asthma, Allergy and Clinical Immunology
2003;23(4):818-825
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Atopic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Several reports have suggested an important role for costimulation through the CD28/CTLA4 (cytotoxic T lymphocyte-associated antigen 4)-B7 (CD80/CD86) pathway in allergen activation of T cells in animal models of allergen-induced asthma, because B7-CD28/ CTLA4 interaction can promote the differentiation and development of the Th2 lymphocyte subset. OBJECTIVE: In the present study, we intended to investigate a potential role of humanized CTLA4-Ig on the inhibition of T and B cell activation by blocking B7/CD28 interactions. METHOD: For this purpose we produced humanized CTLA4-Ig fusion protein by transfection to CHO cell and examined its inhibitory effects for activated T and B cell responses. We evaluated the inhibitory effect of MLR (mixed lymphocyte reaction) and con A-stimulated T cell proliferation. And we assayed wheather B cell was inhibited by stimulation of costimulatory signal in LPS-induced B cell response and PFC assay. RESULT: In vitro assay, humanized CTLA4-Ig fusion protein inhibited T cell-specific immune response in dose-dependent manner: CTLA4-Ig inhibited allogeneic stimulation in murine MLR, and the proliferation of T cell by the stimulation of Con A. But CTLA4-Ig did not inhibit directly the proliferative response of B cell by the stimulation of LPS. In addition, in vivo assay, CTLA4-Ig inhibited the production of antibody from B cell, which was presented by plaque-forming cell (PFC) assay. CONCLUSION: These findings suggest that humanized CTLA4-Ig is effective to inhibit the proliferation of activated T cell directly by blocking B7/CD28 costimulation. And humanized CTLA4-Ig influences antibody-producing capacity of B cell indirectly by regulating T cell.
