CD45RO+ memory T cells but not CD45RA+ naive T cells can be efficiently activated by remote co-stimulation with B7.
Co-stimulatory signals are absolutely required for T cell activation after TCR-MHC-peptide interaction. The most important co-stimulatory signal known so far is mediated by the interaction of CD28 on T cells with B7 on APC. Here we demonstrate that the co-stimulatory signal from the B7 molecule does not necessarily have to come from the same cell which presents antigen. Titration curves obtained by limiting the amount of anti-CD3 mAb suggests that the same amount of TCR-CD3 cross-linking is required for full T cell activation whether B7 is present on the same or on another cell, but that the kinetics of T cell activation is slower when B7 is present on a separate cell from the primary signal. Finally and most importantly we also show that CD45RO+ memory T cells, but not CD45RA+ naive T cells, can be efficiently activated when B7 is expressed on bystander cells. These findings imply that co-stimulatory activation requirements of B7 are more stringent for naive than for memory T cells, which could be an important mechanism involved in the maintenance of self-tolerance.
Van de Velde
H
H
Division of Physiology-Immunology, Medical School, Vrije Universiteit Brussels, Belgium.
Lorré
K
K
Bakkus
M
M
Thielemans
K
K
Ceuppens
J L
JL
de Boer
M
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology; D002461:Cell Line, Transformed; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D018122:B7-1 Antigen; D018106:CD28 Antigens; D017493:Leukocyte Common Antigens