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Infection and Immunity, May 2001, p. 3073-3081, Vol. 69, No. 5
Department of Immunology, The Weizmann
Institute of Science,1 and
ProSpec-TechnoGene, Weizmann Science
Park,2 Rehovot, Israel, and
Immunobiological Research Institute Siena (IRIS), 53100 Siena,
Italy3
Received 1 December 2000/Returned for modification 4 January
2001/Accepted 19 February 2001
Pertussis toxin (PT), a holomer consisting of a catalytic S1
subunit and a B oligomer composed of S2-S4 and S3-S4 dimers, held
together by the S5 subunit, exerts profound effects on immune cells,
including T-cell mitogenicity. While the mitogenic activity of PT was
shown to reside fully within the B oligomer, it could not be assigned
to any particular B-oligomer component. In this study, we purified the
S3-S4 dimer to homogeneity under conditions propitious to maintenance
of the native conformation. In contrast to previous reports which
suggested that both S3-S4 and S2-S4 dimers are necessary for mitogenic
activity, our preparation of the highly purified S3-S4 dimer was as
strongly mitogenic as the B oligomer, suggesting that the S3-S4 dimer
accounts for the mitogenic activity of the B oligomer. Moreover, in
vitro stimulation of naive lymphocytes by the S3-S4 dimer resulted in
reversal of the normal CD4+/CD8+ T-cell ratio
from approximately 2:1 to 1:2. The reversal of the CD4+/CD8+ T-cell ratio is unlikely to be due to
preferential apoptosis-necrosis of CD4+ T cells, as
indicated by fluorescence-activated cell sorter analysis of
annexin-stained T-cell subsets, or to preferential stimulation of
CD8+ T cells. The mechanism underlying the reversal
requires further investigation. Nevertheless, the data presented
indicate that the S3-S4 dimer may have potential use in the context of
diseases amenable to immunological modulation.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.5.3073-3081.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Reversal of the CD4+/CD8+
T-Cell Ratio in Lymph Node Cells upon In Vitro Mitogenic Stimulation by
Highly Purified, Water-Soluble S3-S4 Dimer of Pertussis
Toxin
*
Corresponding author. Mailing address: Dept. of
Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Phone: 972-8-9342991. Fax: 972-8-9344141. E-mail:
lcbennun{at}wicc.weizmann.ac.il.
This paper is dedicated to Tany Amarant, who passed away suddenly
on 6 March 2000.
Present address: Mount Sinai Medical Center, New York, NY 10128.
Infection and Immunity, May 2001, p. 3073-3081, Vol. 69, No. 5
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.5.3073-3081.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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