ICAM-2 provides a costimulatory signal for T cell stimulation by allogeneic class II MHC.
To examine the functional role of intercellular adhesion molecule (ICAM)-2 (CD102) in antigen presentation to T cells, the I-E(d)-transfected murine fibroblastic L cell line RT10.3 (H-2(k)) was transfected with murine ICAM-1 or ICAM-2 and tested for their abilities to stimulate C3H/He (H-2(k)) splenic T cells. The expression of ICAM-1 or ICAM-2 on RT10.3 cells significantly increased the stimulation of T cells in an LFA-1 (CD11a/CD18)-dependent manner as determined by thymidine incorporation. This enhanced T cell response was also observed when combinations of untransfected RT10.3 cells and ICAM-1- or ICAM-2-transfected L cells were used as stimulators, indicating that ICAM-1 and ICAM-2 deliver a costimulatory signal instead of merely enhanced T cell adhesion to antigen presenting cells. The T cells stimulated with ICAM-transfected RT10.3 in the primary response vigorously responded to BALB/c (H-2(d)) spleen cells in a secondary allogeneic stimulation. In contrast, T cells stimulated with untransfected RT10.3 in the primary response did not respond to BALB/c spleen cells in the secondary response. Significant secondary responses to a third party stimulator, C57BL/6 spleen cells (H-2(b)), were observed regardless of ICAM expression on RT10.3 cells in the primary stimulation. These results indicate that ICAM-2 as well as ICAM-1 not only enhance antigen presentation mediated by allogeneic class II MHC but also provide a costimulatory signal to T cells. This costimulatory signal may be important in the aversion of an anergic state.
Carpenito
C
C
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Pyszniak
A M
AM
Takei
F
F
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000494:pharmacology*; D007739:L Cells; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; C065289:ICAM2 protein, human; D013755:Tetradecanoylphorbol Acetate