Failure of correlation between B7 expression and activation of interleukin-2-secreting T cells.
It is well established that triggering interleukin-2 (IL-2) secretion by helper T cells requires the T cell to receive at least two discrete signals. One signal is transduced by the CD3 complex, usually as the result of T cell receptor (TcR) occupancy, the second, or co-stimulatory, signal involves a non-cognate interaction between cell surface accessory molecules on the antigen-presenting cell (APC) and the T cell. A molecular interaction that has been implicated in the provision of co-stimulatory signals is that between B7/BB1 on the APC and its ligands, CD28 and CTL-A4 on the T cell. We have studied the ability of HLA-class II antigen-positive human T cells and a population of DR1-expressing transfected human fibroblasts to stimulate a proliferative response by human T cell clones, and by freshly isolated peripheral blood T cells. Despite their high levels of B7 expression, the T cell clones, were unable to induce proliferation or IL-2 secretion by DR-restricted, antigen-specific T cells. In contrast, the DR1-expressing transfectants, that were B7 negative, induced a strong proliferative response. When these two populations of DR-expressing cells were used to stimulate a primary alloresponse the results were reversed, in that the T cell clones induced a strong alloresponse but the transfected fibroblasts induced no proliferation. These results suggest that the expression of B7 may be necessary for costimulation of unprimed T cells, but not of established T cell clones. Furthermore the data show that the expression of B7 by an APC does not necessarily lead to IL-2 production or protection from the induction of tolerance. The mechanisms responsible for the inability of these T cells to provide full activation signals when used as APC is currently under investigation.
Lombardi
G
G
Department of Immunology, Royal Postgraduate Medical School, London, GB.
Sidhu
S
S
Dodi
T
T
Batchelor
R
R
Lechler
R
R
D000938:Antigen-Presenting Cells / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology*; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2