Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes.
Integrins are a superfamily of related molecules whose function, where known, is to mediate adhesion. The so-called very-late-activation antigen (VLA) family includes at least five distinct heterodimers, each composed of a unique alpha-subunit non-covalently associated with a common beta-subunit. Several members of the family have been shown to bind extracellular matrix proteins, but the function of VLA-4 is so far unknown. VLA-4 is the only member of the family detected on thymocytes and resting T cells. We show here that an antibody which recognizes the beta-subunit of VLA-4 (CD29) on T cells can inhibit CD4+ cell proliferation triggered by CD2 or CD3, and that binding of this antibody to activated T cells leads to an increase in cyclic AMP levels which is comparable to that elicited by forskolin. These negative signalling effects are unique to this antibody: other CD29 antibodies do not affect the growth of activated CD4 cells but enhance the proliferation of whole T cell populations and abrogate the suppressive effects of mitomycin-treated CD8 cells on CD4-cell growth. Taken together, our results indicate that VLA-4 functions in cell-cell interactions and that it is the target for the suppressive effects of CD8 cells on CD4 cells.
Groux
H
H
Laboratoire d'Immunologie des Tumeurs de L'Enfant, Institut Gustave-Roussy, Villejuif, France.
Huet
S
S
Valentin
H
H
Pham
D
D
Bernard
A
A
D000943:Antigens, Differentiation / Q000494:pharmacology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D011863:Radioimmunoassay; D016029:Receptors, Very Late Antigen
D000943:Antigens, Differentiation; D016029:Receptors, Very Late Antigen; D000242:Cyclic AMP