       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).

