Differential requirements for co-stimulatory signals from B7 family members by resting versus recently activated memory T cells towards soluble recall antigens.
The interaction between CD28 on T cells with CD80 (B7-1) and CD86 (B7-2) on APCs is considered to be of critical importance for primary T cell activation both in vivo and in vitro. The relative importance of this co-stimulatory signal in memory T cell activation is, however, less clear, and was therefore studied by in vitro experiments on T cell responses to soluble recall antigens using peripheral blood mononuclear cells or T cell clones. Our data demonstrate that B7-2 represents the major co-stimulatory signal for the activation of resting peripheral blood memory T cells with recall antigens, as evidenced by the effects of anti-B7-1 and anti-B7-2 on T cell proliferation as well as on IL-2 and INF-gamma production. Since CTLA-4-lg and anti-CD28 Fab fragments had similar inhibitory effects to the combination of anti-B7-1 plus anti B7-2, the involvement of a third co-stimulatory CD28/CTLA-4 ligand is unlikely. Despite the strong effects of B7-blocking agents, a variable fraction of the memory T cells was resistant to inhibition. Moreover, T cell clones or in vitro preactivated T cells could efficiently be restimulated by soluble atigens on autologous APCs in the absence of B7-1 or B7-2 co-stimulation. These data show that most memory T cells that are freshly isolated from the blood are still dependent on CD28 triggering for their activation. However, recently activated T cells can apparently bypass the requirement for B7 and use other co-stimulatory signals for reactivation, a finding with important implications for the development of immunosuppressive strategies.
Yi-qun
Z
Z
Laboratory of Experimental Immunology, Department of Pathophysiology, Catholic University of Leuven, Leuven, Belgium.
Joost van Neerven
R J
RJ
Kasran
A
A
de Boer
M
M
Ceuppens
J L
JL
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D007371:Interferon-gamma