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B7-CD28 interaction is a late acting co-stimulatory signal for human T cell responses.
- Source :
-
International immunology [Int Immunol] 1997 Aug; Vol. 9 (8), pp. 1095-102. - Publication Year :
- 1997
-
Abstract
- The interaction of CD28 with one of the B7 molecules (CD80 and CD86) on professional antigen-presenting cells (APC) is generally considered as the most important co-stimulatory signal for T cell activation. APC in a resting condition express either no or only low levels of B7 molecules. These are up-regulated as a result of interactions with activated T cells, thus suggesting that B7-CD28 interaction is not required at initiation of T cell activation. To study this issue, we blocked B7-CD28 interaction at various time points after in vitro stimulation of peripheral blood T cells with allogeneic monocytes. Epstein-Barr virus-transformed B cells or soluble antigens. We observed that T cell proliferation and IL-2 production were inhibited by B7-blocking agents (CTLA-4-Ig or anti-B7 mAb) almost to the same degree when added either at initiation of culture or 24 h later. B7-blocking agents still resulted in significant inhibition of allogeneic T cell activation when added after 48 h. Furthermore, when CTLA-4-Ig was added at the start of an allogeneic T cell stimulation, addition of anti-CD28 mAb after 24 h of culture nearly fully restored T cell proliferation to control levels. Finally, we demonstrate that delayed addition of B7-blocking agents together with cyclosporin A 1 day after the onset of culture of T cells with allogeneic B cells is highly efficient to induce energy as evaluated by lack of proliferation, cytotoxic T lymphocyte reactivity and IFN-gamma or IL-5 production upon alloantigen rechallenge. Taken together, our data can explain why B7 expression on APC is not required at the time of initial APC-T cell contact, and suggest that the effect of the CD28 signal indeed consists in prolonging IL-2 production and amplifying T cell responses, rather than in providing a critical co-stimulatory signal at the time of initial TCR triggering.
- Subjects :
- Abatacept
Antigens, CD
B7-1 Antigen metabolism
CD28 Antigens metabolism
CTLA-4 Antigen
Cell Count
Clonal Anergy
Humans
Interleukin-2 metabolism
Time Factors
Antigen-Presenting Cells immunology
Antigens, Differentiation metabolism
B7-1 Antigen immunology
CD28 Antigens immunology
Cytokines metabolism
Immunoconjugates
Lymphocyte Activation immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0953-8178
- Volume :
- 9
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- International immunology
- Publication Type :
- Academic Journal
- Accession number :
- 9263006
- Full Text :
- https://doi.org/10.1093/intimm/9.8.1095