A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other co-stimulatory molecules.
T cell activation requires two signals: a signal from the TCR and a co-stimulatory signal provided by antigen-presenting cells (APC). In addition to CD28, multiple molecules on the T cell have been described to deliver co-stimulatory signals. Here, we investigated whether there exist quantitative or qualitative differences in the co-stimulatory capacity between CD28 and other molecules. Anti-CD28 monoclonal antibody (mAb) and mAb against CD5, CD9, CD2, CD44 or CD11a all induced activation of naive T cells in the absence of APC when co-immobilized with a submitogenic dose of anti-CD3 mAb. [3H]Thymidine incorporation determined 2 days after co-stimulation was all comparable. In contrast to progressive T cell proliferation induced by CD28 co-stimulation, co-stimulation by other T cell molecules led to a decrease in viable cell recovery along with the induction of apoptosis of once activated T cells. This was associated with a striking difference in IL-2 production; CD28 co-stimulation induced progressively increasing IL-2 production, whereas co-stimulation by other molecules produced limited amounts of IL-2. Addition of recombinant IL-2 to the latter cultures corrected the induction of apoptosis, resulting in levels of cellular proliferation comparable to those observed for CD28 co-stimulation. These results indicate that a fundamental difference exists in the nature of co-stimulation between CD28 and other molecules, which can be evaluated by the levels of IL-2 production, but not simply by [3H]thymidine incorporation.
Yashiro
Y
Y
Biomedical Research Center, Osaka University Medical School, Japan.
Tai
X G
XG
Toyo-oka
K
K
Park
C S
CS
Abe
R
R
Hamaoka
T
T
Kobayashi
M
M
Neben
S
S
Fujiwara
H
H
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D017209:Apoptosis; D018801:CD2 Antigens / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology; D018956:CD5 Antigens / Q000502:physiology; D002453:Cell Cycle; D018960:Hyaluronan Receptors / Q000502:physiology; D019012:Integrin beta1 / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D060245:Tetraspanin 29
D015703:Antigens, CD; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D018956:CD5 Antigens; C554870:Cd9 protein, mouse; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29