CD40L is important for induction of, but not response to, costimulatory activity. ICAM-1 as the second costimulatory molecule rapidly up-regulated by CD40L.
The CD40 ligand (CD40L):CD40 interaction plays an important role in the activation of both T and B cells. However, the mechanisms by which this interaction is involved in activation of T cells is still unclear. Here we show that CD40L is not essential for T cell response to TCR engagement if the APC have costimulatory activity, although it is essential for T cell-mediated induction of such costimulatory activity. To determine the molecular basis of this activity, we have produced three mAbs that appear to recognize the costimulatory molecules rapidly induced by CD40L. Two of them recognize CD44H, which we showed to have CD28-independent costimulatory activity for T cells. The molecule recognized by the remaining mAb is hereby identified as ICAM-1. Furthermore, ICAM-1-mediated costimulation is likely to serve for a function similar to that mediated by the B7:CD28 interaction, as targeted mutation of CD28 renders T cell responses to Con A more dependent on ICAM-1.
Shinde
S
S
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA.
Wu
Y
Y
Guo
Y
Y
Niu
Q
Q
Xu
J
J
Grewal
I S
IS
Flavell
R
R
Liu
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018106:CD28 Antigens / Q000235:genetics; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D016853:Muromonab-CD3 / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand