The vitronectin receptor serves as an accessory molecule for the activation of a subset of gamma/delta T cells.
Constitutive production of cytokines was observed in 3 of 12 gamma/delta T cell lines derived from murine epidermis and correlated with the expression of the C gamma 4, V delta 6 T cell receptor (TCR). After adaptation of one of the lines (T195/BW) to serum-free culture conditions, cessation of the "spontaneous" production of interleukin 4 (IL-4) was observed and IL-4 production could then by induced by the addition of RGD-containing extracellular matrix (ECM) proteins to the culture. The response to the ECM proteins could be completely inhibited by a mAb to the murine vitronectin receptor (VNR). However, the induction of IL-4 production could also be inhibited by anti-CD3 and by an anti-clonotypic mAb to the TCR-gamma/delta of T195/BW. As TCR-gamma/delta loss mutants of T195/BW also failed to respond to ECM proteins, these data demonstrate that engagement of the VNR by its ligand is necessary, but not sufficient, for the induction of IL-4 production. Furthermore, the VNR is expressed by many other T cell clones (both gamma/delta and alpha/beta), none of which produce lymphokines constitutively. Taken together, these observations strongly favor the view that not only is coexpression of the VNR and TCR required for the induction of IL-4 production, but that the TCR must also be engaged by its ligand, most likely a cell surface antigen expressed by the hybridoma itself.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
K
K
Roberts
W M
WM
Yokoyama
P J
PJ
Kehn
E M
EM
Shevach
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D000078404:Epidermal Cells; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000502:physiology; D016023:Integrins / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic / Q000502:physiology*; D019030:Receptors, Vitronectin; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D016023:Integrins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D019030:Receptors, Vitronectin