Activation via the CD3 and CD16 pathway mediates interleukin-2- dependent
autocrine proliferation of granular lymphocytes in patients with granular
lymphocyte proliferative disorders
S Hoshino, K Oshimi, M Teramura and H Mizoguchi
Department of Medicine, Tokyo Women's Medical College, Japan.
Granular lymphocytes (GLs) in patients with GL-proliferative disorders
(GLPDs) are known to express the interleukin-2 receptor (IL-2R) beta chain
(p70-75) constitutively and to proliferate in response to stimulation with
IL-2 via the beta chain. In this report, we found that the anti-CD3
monoclonal antibody (MoAb) OKT3 could induce the proliferation of GLs from
patients with T-cell lineage GLPDs (T-cell receptor-alpha beta+/CD3+16+),
but not that of natural killer (NK) cell lineage GLs (T-cell receptor-alpha
beta-/CD3-16+). In contrast, the anti-CD16 MoAb 3G8 that reacts with
NK-lineage GLs could induce the proliferation of these GLs but not that of
GLs with a T-cell phenotype. Furthermore, the anti-CD16 MoAbs CLB FcR gran1
(VD2) and OK-NK, which react with both T- and NK-lineage GLs, induced the
proliferation of GLs with both T- and and NK-cell phenotypes. The
proliferative response induced via the CD3 or IgG Fc receptor III (Fc gamma
RIII: CD16) pathway was shown to be associated with the IL-2-dependent
autocrine pathway by various findings, including the induction of
endogenous IL-2 production, the coexpression of the IL-2R alpha chain (p55)
and the IL- 2R beta chain, and the inhibition of GL proliferation by
anti-IL-2 or anti-IL-2R MoAb. These results suggest that GL proliferation
is mediated at least partly through the IL-2-dependent autocrine pathway,
and that the TCR/CD3 complex in T-cell phenotype GLs and the Fc gamma RIII
in both T- and NK-cell phenotype GLs play a role in their activation in
GLPDs.
Volume 78,
Issue 12,
pp. 3232-3240,
12/15/1991
Copyright © 1991 by The American Society of Hematology
