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M9630162.TXT
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1996-02-27
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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).