CD11a/CD18 (LFA-1) integrin engagement enhances biosynthesis of early cytokines by activated T cells.
To study the signaling role of CD11a/CD18 in the early events of T cell activation we have examined the induction of transcription of two important cytokines, namely TNF alpha and IL-2. Human peripheral blood T cells were stimulated with PMA/ionophore or immobilized anti-CD3 mAb (OKT3) with or without CD11a/CD18 engagement. Induced cytokine production by immobilized OKT3 was enhanced (3- to 10-fold) in cells adhering to OKT3 and ICAM-1 coimmobilized surfaces and anti-CD11a mAb abolished this enhancement effect. Similarly, inhibition of the PMA/ionophore-induced CD11a/CD18-mediated homotypic aggregations of T cells by mAbs specific for either CD11a or ICAM-1 reduced the induced cytokine production by more than 70%. We have also observed that greatly enhanced cytokine production resulted from cellular interactions between activated T cells and monolayers of endothelial cells. This enhancement was inhibited by a combination of CD11a-, CD18-, and ICAM-1-specific mAbs implicating a role of CD11a/CD18 in leukocyte adhesion to endothelium and diapedesis as part of the inflammatory process. By Northern analyses induced TNF alpha mRNA expression was significantly enhanced by the engagement of CD11a/CD18 in all the conditions mentioned above. These results, together with our previous studies on monocytes, lead to the conclusion that engagement of the CD11/CD18 family of receptors results in the transduction of cellular signals that quantitatively enhance the expression of important leukocyte-mediated immune and inflammatory responses.
Fan
S T
ST
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Brian
A A
AA
Lollo
B A
BA
Mackman
N
N
Shen
N L
NL
Edgington
T S
TS
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D016853:Muromonab-CD3; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016853:Muromonab-CD3; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1