Cm. Ausiello et al., CD38 LIGATION INDUCES DISCRETE CYTOKINE MESSENGER-RNA EXPRESSION IN HUMAN CULTURED LYMPHOCYTES, European Journal of Immunology, 25(5), 1995, pp. 1477-1480
Human CD38 is a surface glycoprotein expressed by different immune-com
petent cells such as immature and activated lymphocytes, plasma cells
and natural killer cells. It has recently been reported that the CD38
molecule exerts adenosine diphosphate ribosyl cyclase activity and is
associated with distinct transmembrane signaling molecules. This study
reports that ligation of CD38 by specific monoclonal antibodies (mAb)
induces multiple cytokine mRNA expression in cultured peripheral bloo
d mononuclear cells (PBMC). The mRNA for tumor necrosis factor-alpha,
interleukin (IL)-1 beta, IL-6, granulocyte-macrophage colony-stimulati
ng factor (GM-CSF) and LL-12 were always detected, whereas interferon-
gamma and IL-10 mRNA expression were seen in most, but not all PBMC cu
ltures. Low levels of IL-2, IL-4 and IL-5 mRNA were also found. The ke
y observation of this work is that CD38 ligation in PBMC induces a lar
ge spectrum of cytokines, many of which overlap with those induced via
CD3 activation. The main differences between CD38 and CD3 activation
are the low to undetectable levels of IL-2 mRNA, and the sustained IL-
1 beta and IL-6 mRNA accumulation found in PBMC cultures following tre
atment with anti-CD38 mAb. Furthermore, PBMC proliferation was not fou
nd to be a prerequisite for CD38-mediated cytokine induction. Together
, these results suggest that human CD38 activates a signaling pathway
which leads to the induction of a discrete array of cytokines, and tha
t this pathway only partially overlaps with that controlled by T cell
receptor CD3.