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T helper-independent activation of human CD8+ cells: the role of CD28 costimulation.
Van Gool SW; Zhang Y; Kasran A; de Boer M; Ceuppens JL; Department of
October 30, 1996
Scand J Immunol. 1996 Jul;44(1):21-9. Unique Identifier : AIDSLINE

The concept that activation of MHC class I-restricted CD8+ cells entirely depends on help from MHC class II-restricted CD4+ T cells has recently been supplemented with an alternative model in which CD8+ 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+ T cells in two different in vitro models. Freshly isolated CD8+ cells could be activated (proliferation, IL-2 production and cytotoxic activity) by anti-CD3-presenting Fc gamma R+ mouse cells transfected with the human CD28 ligand, CD80, as the only accessory signal. On the other hand, activation of CD8+ 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+ cells in the MLR with allogeneic B-cell lines. This combination also induced non-responsiveness of CD8+ cells upon restimulation in the absence of blocking agents. Therefore, although professional APC can apparently provide multiple costimulatory signals for direct activation of CD8+ T cells, the signal derived from CD80/CD86 is unique in providing CsA-resistance.

Adult Antibodies, Monoclonal/PHARMACOLOGY Antigens, CD28/IMMUNOLOGY/METABOLISM/*PHARMACOLOGY Antigens, CD80/PHARMACOLOGY Antigens, Differentiation/PHARMACOLOGY Cell Separation Cells, Cultured Clonal Anergy Cyclosporine/PHARMACOLOGY Cytotoxicity, Immunologic/DRUG EFFECTS CD8-Positive T-Lymphocytes/DRUG EFFECTS/*IMMUNOLOGY Drug Synergism Epitopes/PHARMACOLOGY Female Human Immunosuppressive Agents/PHARMACOLOGY Isoantigens/PHARMACOLOGY Ligands Lymphocyte Culture Test, Mixed *Lymphocyte Transformation/DRUG EFFECTS Male Middle Age Receptors, Interleukin-2/BIOSYNTHESIS Support, Non-U.S. Gov't T-Lymphocytes, Cytotoxic/IMMUNOLOGY T-Lymphocytes, Helper-Inducer/*IMMUNOLOGY JOURNAL ARTICLE