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Document 0047
DOCN M9630047
TI Contrasting in vivo effects on T helper cell functions induced by
mitogenic (intact) versus nonmitogenic (F(ab')2) anti-CD3 monoclonal
antibody.
DT 9603
AU Sawchuk SS; Gates R; Hirsch R; William S. Rowe Division of Rheumatology,
Children's Hospital; Medical Center, University of Cincinnati, Ohio
45229, USA.
SO Transplantation. 1995 Dec 15;60(11):1331-7. Unique Identifier : AIDSLINE
MED/96106496
AB Anti-CD3 mAbs are potent inhibitors of T cell function; however,
administration of mitogenic mAb can cause significant morbidity
secondary to T cell activation and cytokine release. Nonmitogenic
anti-CD3 mAb is immunosuppressive in mice without inducing detectable
morbidity, and may thus be preferable for in vivo T cell
immunosuppression. The precise mechanisms of action of these two forms
of mAb have not been fully defined. To further characterize and compare
the in vivo functional effects of mitogenic and nonmitogenic anti-CD3
mAbs, mice were treated with the intact (mitogenic) form of the
anti-murine CD3 mAb, 2C11, or with F(ab')2 fragments (nonmitogenic).
Effects on T cell phenotypes and the secretion of Th1-derived cytokines
were compared. Nonmitogenic mAb induced a prolonged downregulation of
secretion of interleukin (IL)-2 and interferon (IFN)-gamma from CD4+ T
cells, and of IL-2 secretion from CD8+ T cells, and preferential
depletion of CD4+ T cells. In marked contrast, mitogenic mAb induced a
prolonged upregulation of IL-2 and IFN-gamma secretion from both CD4+
and CD8+ cells, and preferential depletion of CD8+ T cells. Both forms
of mAb induced a shift in the T cell populations from a naive to a
memory phenotype; however, this shift was not responsible for the
observed changes in cytokine secretion. These results demonstrate that
mitogenic and nonmitogenic forms of 2C11, while binding to the identical
epitope, differentially affect T cell functions, and have implications
for the use of anti-CD3 mAbs in the clinical setting.
DE Animal Antigens, CD3/*PHYSIOLOGY Cytotoxicity, Immunologic CD4-CD8
Ratio CD8-Positive T-Lymphocytes/*IMMUNOLOGY Down-Regulation
(Physiology) Immunoglobulins, Fab/IMMUNOLOGY Immunologic Memory
Interferon Type II/*SECRETION Interleukin-2/*SECRETION *Lymphocyte
Transformation Male Mice Mice, Inbred C57BL Spleen/CYTOLOGY
Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocyte
Subsets/IMMUNOLOGY Th1 Cells/*IMMUNOLOGY Up-Regulation (Physiology)
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).