Activation induced changes in expression and structure of the IL-7 receptor on human T cells.
Activation of human peripheral blood T cells renders them capable of proliferating to IL-2, -4, and -7, and upregulates the receptors for IL-2 and -4. In this study the effect of activation on the receptor for IL-7 has been investigated. Scatchard analysis showed dual affinity binding of IL-7 to peripheral blood mononuclear cells (PBMC). Furthermore, activation of PBMC with anti-CD3 antibodies resulted in a 4-fold downregulation of both the high and low affinity IL-7 receptors. SDS-PAGE analysis of [125I]IL-7 cross-linked resting PBMC revealed a major complex of 104/107 kDa (reduced/non-reduced) and a minor complex of 184/178 kDa (reduced/non-reduced). In contrast, cross-linking of activated PBMC revealed a third prominent complex of 93 kDa (non-reduced) not seen on unstimulated cells. This 93 kDa complex was observed on purified activated peripheral blood T cells and T cell blasts. Moreover, on a panel of IL-7 responsive T cell clones the 93 kDa complex was the only major cross-linked product observed. These results demonstrate that T cell activation causes changes in both the level of expression of the IL-7 receptor and the nature of the proteins associated with the receptor. It is postulated that these changes in receptor structure may be related to the acquisition of responsiveness to the IL-7 growth signal.
Foxwell
B M
BM
Charing Cross Sunley Research Centre, Hammersmith, London, UK.
Taylor-Fishwick
D A
DA
Simon
J L
JL
Page
T H
TH
Londei
M
M
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D020395:Receptors, Interleukin-7; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7