JCI96b J. Clin. Invest. 1996. 98:2616-2622.
Stimulated Human Lamina Propria T Cells Manifest Enhanced Fas-Mediated Apoptosis

Monica Boirivant *, Roberta Pica# , Ruggero De Maria^, Roberto Testi^, Francesco Pallone@ and Warren Strober$

* Immunology Department, Istituto Superiore di Sanita', Rome, Italy, #GI Unit, II Clinica Medica, Universita' "La Sapienza", Rome, Italy, ^Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", Rome, Italy; @Department of Experimental Medicine, University of Reggio Calabria, Catanzaro, Italy, $ Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland, USA.

Corresponding author: Monica Boirivant

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 co-stimulatory 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 non-stimulatory 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 signalling pathway. Given that INF-g secretion is significantly increased in LP T cells in which apoptosis is inhibited, this feature of LP T cells may present a mechanism of regulating detrimental immune responses in the mucosal enviroment.