Jt. Kung et al., LYMPHOKINE REGULATION OF ACTIVATION-INDUCED APOPTOSIS IN T-CELLS OF IL-2 AND IL-2R-BETA KNOCKOUT MICE, Cellular immunology, 185(2), 1998, pp. 158-163
Recent studies using IL-2R alpha knockout mice have generated conflict
ing results regarding the hypothesis that IL-2/IL-2R interaction is ob
ligatory for the development of AICD, which plays a central and pivota
l role in maintaining peripheral tolerance. A relevant consequence of
AICD defect is the demonstrated development of autoimmune lymphoprolif
erative disease in IL-2, IL-2R alpha, and IL-2R beta knockout mice, bu
t not in IL-4, IL-7, or IL-7R knockout mice. Whether IL-4, IL-7, or IL
-15 can provide the required signal for AICD development is addressed
here using IL-2 and IL-2R beta knockout mice. Lymph node T cells from
knockout mice were stimulated with Con A plus rIL-1 for 3 days and the
n maintained in high concentrations of rIL-4, rIL-7, or rIL-15 for an
additional 3 days before they were subjected to AICD analysis. Our stu
dy demonstrates that IL-4, IL-7, and IL-15 can transduce signals criti
cal for AICD development in the absence of IL-2-mediated signals. The
requirement for relatively high concentrations of these lymphokines su
ggests their limited role in maintaining peripheral T cell tolerance,
thus explaining the differential expression of autoimmune lymphoprolif
erative disease in the targeted mutant strains described above. (C) 19
98 Academic Press.