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T Helper-Independent Activation of Human CD8+ Cells: the Role of CD28 Costimulation.
- Source :
- Scandinavian Journal of Immunology; Jul1996, Vol. 44 Issue 1, p21-29, 9p, 5 Graphs
- Publication Year :
- 1996
-
Abstract
- The concept that activation of MHC class I-restricted CD8<superscript>+</superscript> cells entirely depends on help from MHC class II-restricted CD4<superscript>+</superscript> T cells has recently been supplemented with an alternative model in which CD8<superscript>+</superscript> cells can directly be activated by MHC class I-expressing professional antigen-presenting cells (APC), which are able to deliver an accessory signal. The authors analysed the role of CD28-mediated costimulation for T helper cell-independent activation of purified human CD8<superscript>+</superscript> T cells in two different <em>in vitro</em> models. Freshly isolated CD8<superscript>+</superscript> cells could be activated (proliferation, IL-2 production and cytotoxic activity) by anti-CD3-presenting FcγR<superscript>+</superscript> mouse cells transfected with the human CD28 ligand, CD80, as the only accessory signal. On the other hand, activation of CD8<superscript>+</superscript> cells by allogeneic MHC class I on EBV-transformed B cells, which express two different CD28 ligands, CD80 and CD86, also proceeded very efficiently (proliferation, cytotoxic activity and CD25 expression), but was either not, or only partially, blocked by anti-CD80 and anti-CD86 MoAb or CTLA-4Ig. This indicates that other costimulatory signals are also effective, and that CD28 triggering is not absolutely required for initial T-cell activation. CsA and CD80/CD86-blocking agents were synergistic in completely inhibiting activation of CD8<superscript>+</superscript> cells in the MLR with allogeneic B-cell lines. This combination also induced non-responsiveness of CD8<superscript>+</superscript> cells upon restimulation in the absence of blocking agents. Therefore, although professional APC can apparently provide multiple costimulatory signals for direct activation of CD8<superscript>+</superscript> T cells, the signal derived from CD80/CD86 is unique in providing CsA-resistance. [ABSTRACT FROM AUTHOR]
- Subjects :
- MHC antibodies
CELLS
T cells
ANTIGEN presenting cells
MICE
Subjects
Details
- Language :
- English
- ISSN :
- 03009475
- Volume :
- 44
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Scandinavian Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 18728019
- Full Text :
- https://doi.org/10.1046/j.1365-3083.1996.d01-82.x