Alterations in tyrosine kinase dependent signal transduction correlate with functional anergy in T lymphocytes
Abstract
Normal CD4$\sp{+}$ Th1 clones can become functionally inactivated by ligation of T cell antigen receptor (TCR/CD3 complexes in the absence of functional antigen presenting cells (APCs). These cells show proliferative nonresponsiveness, or anergy, in response to antigen restimulation with functional APCs and this nonresponsiveness is due to the lack of IL-2 production. Recently, signal transduction through tyrosine phosphorylation has been suggested to be important in T cell activation. We have shown that anergic Th1 cells express altered levels of protein tyrosine kinases: a decrease in p56$\sp{\rm lck}$ (lck) and an increase in p59$\sp{\rm fyn}$ (fyn). Therefore, the possibility of alterations in tyrosine phosphorylation in anergic cells upon stimulation also was analyzed. By comparing the patterns of tyrosine phosphorylation of control vs. anergic cells upon antigen restimulation, we detected significant decreases in tyrosine phosphorylation of 38kDa (p38) and 74kDa (p74) proteins in anergic cells. Defective tyrosine phosphorylation of p38 and p74 was also detected after CD3 crosslinking in anergic cells. Defective tyrosine phosphorylation of another protein, of 34kDa (p34), was found in anergic cells after CD4 crosslinking. Both the alterations in expression levels of lck and fyn and defective tyrosine phosphorylation were reversed to normal after anergic cells recovered from nonresponsiveness by growth in exogenous IL-2. In addition, normal CD4$\sp{+}$ and CD8$\sp{+}$ T cells tolerized in vivo also showed defective tyrosine phosphorylation of p38 and p74 after CD3 crosslinking. These results demonstrate that changes in tyrosine phosphorylation dependent events correlate well with the lack of IL-2 production and may be responsible for the maintenance of nonresponsiveness in anergic T cells.
Subject Area
Immunology|Cellular biology|Biochemistry
Recommended Citation
Cho, Eun Ah, "Alterations in tyrosine kinase dependent signal transduction correlate with functional anergy in T lymphocytes" (1994). Dissertations available from ProQuest. AAI9521011.
https://repository.upenn.edu/dissertations/AAI9521011