Specific regulation of VLA-4 and alpha 4 beta 7 integrin expression on human activated T lymphocytes.
Modulation of VLA integrins was studied in several human T cell clones upon specific and nonspecific cellular activation. Human activated T lymphocytes down-regulated both alpha 4 beta 1 and alpha 4 beta 7 integrins upon specific recognition of alloantigens (cytotoxic T cells) or in the presence of Staphylococcus enterotoxin B (superantigen recognizing noncytotoxic T cells). In contrast, the expression of other membrane integrins, such as VLA-1 and VLA-5 integrins, was not modified. Down-regulation of alpha 4 beta 1 and alpha 4 beta 7 integrins was observed as early as 3 h after stimulation, lasted later than 72 h and was partially inhibited by cytochalasin D. Interestingly, neither target cells nor NK cells modulated CD49d expression after interaction with T cells of K562, respectively, suggesting that CD49d expression was linked to specific T cell activation. The down-regulation of the CD49d chain in T cell clones stimulated with immobilized anti-CD3 mAbs confirmed the role of TCR-mediated activation in CD49d regulation. However, the CD3-independent cellular aggregation induced by soluble anti-CD43 mAb was also able to strongly down-regulate alpha 4 beta 1 and alpha 4 beta 7. The present work shows the first evidence that CD49d subunit-bearing integrin expression is distinctly regulated from other integrins after Ag or superantigen recognition by human activated T cells. CD49d modulation may be relevant for the traffic and tissue localization of locally activated T cells during immune responses.
Hernández-Caselles
T
T
Department of Biochemistry B and Immunology, Faculty of Medicine, University of Murcia, Spain.
Martínez-Esparza
M
M
Lazarovits
A I
AI
Aparicio
P
P
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D017252:CD3 Complex / Q000502:physiology; D002460:Cell Line; D002999:Clone Cells; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D016023:Integrins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018089:Superantigens / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D017252:CD3 Complex; D039041:Integrin alpha4beta1; D016023:Integrins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing; D018089:Superantigens; C071777:integrin alpha4beta7; D039441:Integrin alpha4; D015638:Cytochalasin D