LFA-1 contributes to signal I of T-cell activation and to the production of T(h)1 cytokines.
The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the proliferation of CD18(-/-) T cells was significantly reduced, whereas cytokine production remained impaired. The diminished proliferative capacity of CD18(-/-) T cells could be fully compensated for by additional triggering of the T-cell receptor, but not by additional stimulation through the costimulatory molecule, CD28. Thus, ligation of LFA-1 on T cells participates in regulation of Th1 cytokines in vivo. In addition, LFA-1 primarily exerts an effect as an enhancer of TCR signalling and does not facilitate classical costimulation.
Varga
Georg
G
Department of Dermatology, University of Muenster, Muenster, Germany. varga@uni-muenster.de
Nippe
Nadine
N
Balkow
Sandra
S
Peters
Thorsten
T
Wild
Martin K
MK
Seeliger
Stephan
S
Beissert
Stefan
S
Krummen
Mathias
M
Roth
Johannes
J
Sunderkötter
Cord
C
Grabbe
Stephan
S
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016747:Minor Lymphocyte Stimulatory Antigens / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D018821:CD18 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016747:Minor Lymphocyte Stimulatory Antigens; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma