Document 0902
 DOCN  M9650902
 TI    CD44 plays a co-stimulatory role in murine T cell activation: ligation
       of CD44 selectively co-stimulates IL-2 production, but not proliferation
       in TCR-stimulated murine Th1 cells.
 DT    9605
 AU    Sommer F; Huber M; Rollinghoff M; Lohoff M; Institute of Clinical
       Microbiology, University of; Erlangen-Nurnberg, Germany.
 SO    Int Immunol. 1995 Nov;7(11):1779-86. Unique Identifier : AIDSLINE
       MED/96162436
 AB    The murine CD44 receptor family is thought to be involved in a variety
       of lymphocyte functions, including lymphopoesis, lymphocyte homing and
       cell migration. Herein, we show that murine CD44 also plays a role as a
       co-stimulatory molecule for the activation of CD4+ T cells. Ligation of
       CD44 by mAb enhanced IL-2 production of long-term cultured,
       anti-CD3-stimulated Th1 cell lines. Moreover, anti-CD44 mAb synergized
       with anti-CD28 mAb in exerting this effect. A synergism of anti-CD28 and
       anti-CD44 mAb to co-stimulate IL-2 production was also observed in
       anti-CD3-triggered, freshly isolated splenic CD4+ T cells. Blocking
       experiments with cyclosporin A indicated that the intracellular pathways
       used by the CD28 and CD44 molecules appear to be different. In contrast
       to the effects on the IL-2 production of Th1 cells, neither anti-CD44
       mAb alone nor the combination of anti-CD44 with anti-CD28 were able to
       induce proliferation of anti-CD3-triggered Th1 cells. In accordance,
       triggering of CD44 and/or CD28 by mAb was not sufficient to reverse the
       previously described 'proliferative block'. This term describes the
       unresponsiveness of Th1 cells against IL-2, which occurs when Th1 cells
       are triggered by anti-CD3 in the absence of co-signals. These data lead
       us to propose a model of Th1 cell activation which includes two
       functionally different types of co-signals: one for IL-2 production and
       a separate one for proliferation.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY/*METABOLISM/PHARMACOLOGY
       Antigens, CD28/IMMUNOLOGY  Antigens, CD3/IMMUNOLOGY  Antigens,
       CD44/IMMUNOLOGY/*METABOLISM/*PHYSIOLOGY  Cell Line  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  Female  Interleukin-2/*BIOSYNTHESIS  Ligands
       *Lymphocyte Transformation  Mice  Mice, Inbred BALB C  Signal
       Transduction/IMMUNOLOGY  Spleen  Support, Non-U.S. Gov't  Th1
       Cells/*IMMUNOLOGY/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).