Mitogenic CD2 monoclonal antibody pairs predispose peripheral T cells to undergo apoptosis on interaction with a third CD2 monoclonal antibody.
When stimulated for a few days with the mitogenic GT2 + T11(1) CD2 mAb pair and IL-2, resting T cells were induced to proliferate but the introduction into the cultures of a third CD2 mAb resulted in apoptotic cell death of 40 to 60% of the cells. The death signal was active on T cells entered the cell cycle without causing an apparent cell cycle block and without discriminating between the G1 and S phases. Apoptosis was not prevented by cycloheximide or actinomycin D, indicating that the death program was already expressed in preactivated cells awaiting an appropriate signal. A series of Abs, directed at various cell surface molecules, were unable to trigger apoptosis (except CD3 mAb), whereas most of the CD2 mAb tested were active, provided the third CD2 mAb was recognizing an epitope different from GT2 and T11(1). Mere aggregation of CD2 molecules did not seem to be the triggering signal of apoptosis, because cross-linking cell-bound GT2 + T11(1) with an Ab to mouse IgG had no effect, suggesting that a conformational change was imposed on CD2 molecules by the third CD2 mAb. Stimulation performed in the presence of IL-2 predisposed both CD45R0+ and CD45RA+ T cells to apoptosis, whereas stimulation in the presence of IL-4 primed only CD45RA+ T cells to undergo this process. Monocytes and potent co-signals of the CD2 pathway were unable to prevent CD2-induced apoptosis. Thus, successive engagements of the CD2 molecule of mature T cells by two and three CD2 mAbs recognizing distinct epitopes can provide in short term cultures signals for proliferation and apoptosis, depending on the activation state of the cells.
Rouleau
M
M
Cellular Immunology and Transplantation Laboratory, Scientific Cancer Research Institute, Villejuif, France.
Mollereau
B
B
Bernard
A
A
Metivier
D
D
Rosenthal-Allieri
M A
MA
Charpentier
B
B
Senik
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017209:Apoptosis; D018801:CD2 Antigens; D002453:Cell Cycle; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D011971:Receptors, Immunologic / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D011971:Receptors, Immunologic; D017493:Leukocyte Common Antigens