Regulation of T-cell differentiation by CD2 and CD28 accessory molecules.
It was analysed to what extent the functional T-cell responses that result from T-cell receptor (TcR)/CD3 triggering differ from responses that are induced after simultaneous ligation of CD2 and CD28 accessory molecules. To allow a quantitative comparison of these activation pathways, purified lymphocytes were stimulated with either graded densities of immobilized anti-CD3 monoclonal antibodies (mAb) or with increasing amounts of anti-CD28 mAb in the presence of a constant concentration of anti-CD2 mAb. Both activation systems were sensitive to the regulatory properties of CD11a/CD18 molecules. T-cell stimulation via CD2/CD28 molecules induced a more potent release of interleukin-2 (IL-2) and more pronounced T helper (Th) cell responses than T-cell stimulation via the TcR/CD3 complex, whereas CD25 expression was more readily initiated after T-cell activation via the TcR/CD3 complex. Optimal Th cell differentiation was detected under conditions of suboptimal receptor occupancy whereas, in contrast, optimal cytolytic T lymphocyte (CTL) differentiation required optimal TcR/CD3 or CD2/CD28 engagement. The findings indicate that T-cell differentiation can be influenced in a qualitative manner by the strength of the activation signal provided, and suggest that antigen-specific T-cell responses might be regulated in a quantitative manner through CD2 and CD28 accessory molecules.
de Jong
R
R
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Stokkers
P
P
Lamme
E
E
Kool
J M
JM
Borst
F
F
Brouwer
M
M
Miedema
F
F
van Lier
R A
RA
D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018845:CD11 Antigens; D018801:CD2 Antigens; D018106:CD28 Antigens; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D018801:CD2 Antigens; D018106:CD28 Antigens; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2