Regulation of CD2-mediated heterotypic interactions of murine T lymphocytes.
In this study we have investigated the expression and function of the murine CD2 receptor in T cells. The surface level of CD2 increased between 300 and 400% when T cells were activated, which also induced a rapid increase of nearly 40-fold in the steady-state levels of CD2 mRNA. Although the activated lymphocytes were found to internalize and degrade nearly 50% of membrane-bound CD2, in addition to shedding the CD2 receptor from the cell surface, this does not account for the discrepancy between the increase in mRNA and antigen levels during activation. These findings suggest that the expression of CD2 is also regulated by post-transcriptional processes which control the translational efficiency of the CD2 message. Activation of T cells enhanced their interaction with mesenchymal cell targets (fibroblasts) via a CD2-dependent adhesion pathway which was not inhibited by the anti-mouse CD48 (sgp-60) mAb OX78, the only counter-receptor thus far identified on other cells as a ligand for the mouse CD2 receptor. Moreover, since murine fibroblasts were found not to express CD48, our results implicate a novel ligand for CD2, possibly a homologue of the human LFA-3. This new pathway of heterotypic T cell interaction would be facilitated by utilization of the large intracellular pool of CD2 transcripts to up-regulate CD2 expression and, as this receptor is a major signal-transducing molecule, would further enhance T cell activation and increase CD2-mediated adhesion.
Abraham
D
D
Cell Enzymology Unit, Kennedy Institute of Rheumatology, Bute Gardens, London, United Kingdom.
Bou-Gharios
G
G
Tulip
G
G
Sumner
H
H
Olsen
I
I
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D018801:CD2 Antigens; D000071178:CD48 Antigen; D002448:Cell Adhesion; D002462:Cell Membrane / Q000276:immunology / Q000648:ultrastructure; D002478:Cells, Cultured; D015870:Gene Expression; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D016253:Microscopy, Immunoelectron; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C000604066:Cd48 protein, mouse; D012333:RNA, Messenger; D011971:Receptors, Immunologic