Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis.
Lamina propria (LP) T cells respond poorly to a proliferative stimulus delivered via TCR/CD3 pathway, but retain considerable ability to respond to a stimulus delivered via CD2 costimulatory or accessory pathway. In the present study, we showed first that unstimulated LP T cells, as compared to unstimulated peripheral blood (PB) T cells, exhibit an increased level of apoptosis which is further increased following CD2 pathway stimulation, but not following via TCR/CD3 pathway stimulation. We next showed that IL-2 had a sparing effect on apoptosis of unstimulated LP T cells in that IL-2 decreased and anti-IL-2 increased apoptosis of these cells; in contrast, IL-2 had no effect on apoptosis of CD2-pathway stimulated cells. Finally, we showed that increased apoptosis of LP T cells induced by CD2-pathway stimulation is inhibited when Fas antigen is blocked by a nonstimulatory anti-Fas antibody. These studies suggest that LP T cells are characterized by increased susceptibility to Fas-mediated apoptosis most due to a downstream change in the Fas signaling pathway. Given that IFN-gamma secretion is significantly increased in LP T cells in which apoptosis is inhibited, this feature of LP T cells may represent a mechanism of regulating detrimental immune responses in the mucosal environment.
Boirivant
M
M
Immunology Department, Istituto Superiore di Sanità, Rome, Italy.
Pica
R
R
DeMaria
R
R
Testi
R
R
Pallone
F
F
Strober
W
W
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D018801:CD2 Antigens / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D018801:CD2 Antigens; D016207:Cytokines; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019014:fas Receptor; D007371:Interferon-gamma