       Document 0162
 DOCN  M9630162
 TI    Pathogenic and protective roles of CD45RB(low) CD4+ cells correlate with
       cytokine profiles in the spontaneously autoimmune diabetic mouse.
 DT    9603
 AU    Shimada A; Rohane P; Fathman CG; Charlton B; Department of Medicine,
       Stanford University School of Medicine,; California, USA.
 SO    Diabetes. 1996 Jan;45(1):71-8. Unique Identifier : AIDSLINE MED/96118417
 AB    The adoptive transfer of splenocytes from diabetic NOD mice to
       NOD-scid/scid (NOD-scid) recipients results in diabetes. This model was
       used to test the effect of cotransfer of splenocyte subsets from young
       nondiabetic NOD mice. As shown previously in other NOD models, the CD4+
       subset from young nondiabetic mice significantly delayed the onset of
       diabetes in splenocyte cotransfers (P < 0.001). The data presented here
       showed that the development of diabetes in NOD-scid recipients
       correlated with a rapid increase in peripheral CD45RB(low) CD4+ cells.
       However, the CD45RB(low) subset of CD4+ cells from young nondiabetic
       mice protected from diabetes transfer in this model. We therefore
       examined whether CD45RB(low) CD4+ cells from diabetic mice were
       pathogenic rather than protective. CD45RB(low) CD4+ splenocytes from
       diabetic NOD mice were transferred along with CD8+ splenocytes from
       diabetic mice into NOD-scid recipients, and all of the recipients became
       diabetic within 5 weeks posttransfer. In contrast, no recipients (0 of
       10) of CD45RB(high) CD4+ cells along with CD8+ splenocytes from diabetic
       mice became diabetic within 5 weeks posttransfer (P < 0.001). A
       correlate for the difference between CD45RB(low) CD4+ cells from
       diabetic NOD mice and CD45RB(low) CD4+ cells from nondiabetic mice,
       which showed protective effect in splenocyte cotransfers, was found in
       cytokine production after stimulation with anti-CD3 antibodies in vitro.
       CD45RB(low) CD4+ cells from diabetic mice showed a significantly higher
       ratio (approximately fivefold) of gamma-interferon (IFN-gamma) to
       interleukin (IL)-4 when compared with CD45RB(low) CD4+ cells from
       nondiabetic mice (P < 0.001). In conclusion, the function of the
       CD45RB(low) population of CD4+ cells changes from a protective to a
       pathogenic one during the development of disease in the NOD mouse. This
       change in function correlates with cytokine production in vitro;
       increased IFN-gamma-to-IL-4 ratio is associated with pathogenic
       potential and occurs coincident with (or after) the onset of diabetes.
 DE    Animal  Antigens, CD45/*PHYSIOLOGY  Autoimmune
       Diseases/ETIOLOGY/*PHYSIOPATHOLOGY  Cytokines/*BIOSYNTHESIS
       CD4-Positive T-Lymphocytes/*PHYSIOLOGY  CD8-Positive
       T-Lymphocytes/PHYSIOLOGY  Diabetes Mellitus,
       Insulin-Dependent/ETIOLOGY/*PHYSIOPATHOLOGY  Female  Flow Cytometry
       Immunotherapy, Adoptive  Inflammatory Bowel Diseases/ETIOLOGY/PATHOLOGY
       Intestine, Large/PATHOLOGY  Male  Mice  Mice, Inbred BALB C  Mice,
       Inbred NOD  Mice, SCID  Severe Combined
       Immunodeficiency/ETIOLOGY/*PHYSIOPATHOLOGY  Spleen/CYTOLOGY  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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

