The number of T cells that have undergone proliferation after antigen stimulation in vivo must be controlled to prevent excessive accumulation of T cells, autoimmunity, and T cell neoplasia. We describe here that primary human adenotonsillar memory phenotype CD45R0 + CD4 + T cells, but not adenotonsillar naive-phenotype CD45RA + CD4 + T cells, or peripheral blood naive or memory CD4 + T cells, express high levels of activation-associated antigens CD38, CD69, CD71, and HLA-DR. These in vivo-activated CD45R0 + CD4 + T cells were susceptible to spontaneous and rapid apoptosis in vitro. Apoptosis could not be inhibited by the disruption of Fas-Fas ligand engagement or by the pan-caspase inhibitor ZVAD. Cross-linking of the T cell antigen receptor did not rescue cells from apoptosis. Apoptosis could be partially inhibited by the chemokine CXCL12/SDF-1, by IL-6, and by the IL-2 receptor common c chain-signaling cytokines IL-2, -7, and -15. Inhibitors of phosphatidylinositol 3-kinase accelerated apoptosis. We conclude that after in vivo activation of CD45R0 + CD4 + T cells, the cells experience a period of intrinsically elevated sensitivity to apoptosis and that multiple external signals control their survival.

Genetic polymorphism of the TGFB1 signal sequence is associated with the response to chemoradiotherapy. TGF-beta1 may sensitize cancer stem cells to chemoradiotherapy.

Reactive oxygen species are toxic to cells but they may also have active roles in transducing apoptotic events. To study the role of reactive oxygen species in growth factor depletion induced apoptosis of human primary CD4+ T cells, we used a synthetic manganese porphyrin superoxide dismutase mimetic to detoxify superoxide anions formed during apoptosis. Apoptosis of primary CD4+ T cells was characterized by generation of superoxide anions, plasma membrane phosphatidyl-serine translocation, loss of mitochondrial membrane potential, activation of caspase 3, condensation of chromatin, as well as DNA degradation. The detoxification of superoxide anions did not influence plasma membrane phosphatidyl-serine translocation, or chromatin condensation, and only marginally inhibited the loss of mitochondrial membrane potential and the formation of DNA strand breaks. In contrast, the detoxification of superoxide anions significantly reduced caspase 3 activity and almost completely inhibited the apoptotic decrease in total cellular DNA content as measured by propidium iodide staining. Our results indicate that reactive oxygen anions induce signals leading to efficient DNA degradation after the initial formation of DNA strand breaks. Thus, reactive oxygen anions have active roles in signaling that lead to the apoptotic events.

The adenoidal epithelial crypt is a potential site of antigen transport from pharyngeal lumen to adenoidal tissue. The base of the crypt is consistently infiltrated with leucocytes, forming a reticular lymphoepithelial structure. To evaluate mechanisms that possibly mediate leucocyte infiltration, expressions of leucocyte adhesion molecules, such as platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31), vascular cell adhesion molecule-1 (VCAM-1) (CD106) and intercellular adhesion molecule-1 (ICAM-1) (CD54), were studied in the adenoidal epithelial crypt. Epithelial cells in the outer opening of the adenoidal crypt were positive for VCAM-1, whereas epithelial cells at the base of the crypt were positive for PECAM-1. Isolated ICAM-1-expressing cells were found throughout the epithelial crypt. Double immunofluorescence staining revealed that the epithelial cells positive for PECAM-1 or VCAM-1 were positive for cytokeratin. The expression of PECAM-1 in the base and VCAM-1 at the orifice of the adenoidal epithelial crypt implies that the base and the orifice of the crypt have a distinct ability to recruit leucocytes. Epithelial cells expressing PECAM-1 may have a role in the formation of the reticular lymphoepithelial structure in the epithelial crypt.