TY - JOUR
T1 - MHC class II molecules regulate growth in human T cells
AU - Nielsen, M
AU - Odum, Niels
AU - Bendtzen, K
AU - Ryder, L P
AU - Jakobsen, B K
AU - Svejgaard, A
N1 - Keywords: Antibodies, Monoclonal; Antigens, CD28; Antigens, CD45; CD4-Positive T-Lymphocytes; Cell Line; HLA-D Antigens; HLA-DP Antigens; HLA-DR Antigens; Humans; Interleukin-2; Lymphocyte Activation; Receptor-CD3 Complex, Antigen, T-Cell; Tetradecanoylphorbol Acetate
PY - 1994
Y1 - 1994
N2 - MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1-like) as well as T cells producing both cytokines (THO-like) responded to class II mAb. The costimulatory effect was not restricted to IL-2-driven T cell growth, since TCR/CD3-induced T cell activation was also enhanced by HLA-DR mAb. Moreover, class II costimulation potentiated CD28-mAb-induced T cell sensitivity to protein kinase C activation by phorbol 12-myristate 13-acetate. In conclusion, class II costimulation enhances T cell activation through the TCR/CD3 and IL-2 pathways and interacts with CD28 accessory signals to up-regulate growth of allospecific T cell lines.
AB - MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1-like) as well as T cells producing both cytokines (THO-like) responded to class II mAb. The costimulatory effect was not restricted to IL-2-driven T cell growth, since TCR/CD3-induced T cell activation was also enhanced by HLA-DR mAb. Moreover, class II costimulation potentiated CD28-mAb-induced T cell sensitivity to protein kinase C activation by phorbol 12-myristate 13-acetate. In conclusion, class II costimulation enhances T cell activation through the TCR/CD3 and IL-2 pathways and interacts with CD28 accessory signals to up-regulate growth of allospecific T cell lines.
M3 - Journal article
C2 - 7913331
SN - 0254-9670
VL - 11
SP - 23
EP - 32
JO - Experimental and Clinical Immunogenetics
JF - Experimental and Clinical Immunogenetics
IS - 1
ER -