T-cell malignancies with mature phenotypes: altered cell cycle regulation
by HLA class I molecules
MC Turco, F Alfinito, M De Felice, A Lamberti, S Ferrone and S Venuta
Dipartimento di Medicina Sperimentale e Clinica, Facolta di Medicina e
Chirurgia, Universita di Catanzaro/Reggio Calabria, Italy.
Soluble anti-HLA class I monoclonal antibodies (MoAbs) modulate normal
T-lymphocyte proliferation induced via the CD3/Ti and the CD2 pathway, but
do not induce proliferation of normal T lymphocytes in the absence of
additional mitogenic stimuli. In this report, we show that anti-HLA class I
MoAbs induce DNA synthesis in peripheral blood mononuclear cells from a
patient with a CD4+CD8+T-prolymphocytic leukemia (T-PLL) and from a patient
with a CD4-CD8+ T-chronic lymphocytic leukemia (T- CLL), in the absence of
detectable additional mitogenic stimuli. Proliferation of leukemic T cells
is induced by both whole Igs and Fab' fragments of anti-HLA class I MoAbs,
arguing in favor of their direct interactions with the proliferating cells
as the mechanism underlying the mitogenic effect. This interpretation is
also supported by the ability of anti-HLA class I MoAbs to induce
proliferation of leukemic T- cell preparations, depleted of accessory
cells. DNA synthesis in T-CLL and T-PLL cells is preceded by expression of
G1-specific messenger RNAs, ie. c-myc, 2F1, Tac, and interferon-gamma, in
activated cells. Cell proliferation is inhibited by the protein kinase C
inhibitor H7, indicating that activation of this enzyme is required for the
mitogenic effect of anti-HLA class I MoAbs. The latter inhibit the
proliferation of T-CLL cells as well as that of normal T cells stimulated
with anti- CD3 MoAbs and enhance that of both types of cells stimulated
with anti- CD2 MoAbs. In addition, anti-HLA class I MoAb Q6/64 in
combination with anti-CD2 MoAb 9.6 or MoAb 9-1 induces proliferation of
leukemic T cells to a greater extent than the individual MoAbs, but is not
mitogenic for normal T cells. Anti-HLA class I MoAbs restore the cytolytic
activity of T-CLL cells that is lost after 5 days of incubation of control
medium, suggesting that HLA class I antigens may mediate a signal
contributing to the activation state. The present results indicate that
leukemic T-cell proliferation can be triggered via HLA class I molecules
and suggest a potential role for these antigens in the in vivo growth of
malignant clones.
Volume 78,
Issue 8,
pp. 2045-2052,
10/15/1991
Copyright © 1991 by The American Society of Hematology
