Faculty Collaboration Database

Dynamic changes in CD4+ CD25+(high) T cell apoptosis after the diagnosis of type 1 diabetes. Clin Exp Immunol 2007 Oct;150(1):75-82

Date

08/23/2007

Pubmed ID

17711492

Pubmed Central ID

PMC2219285

DOI

10.1111/j.1365-2249.2007.03475.x

Scopus ID

2-s2.0-34548534993 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Because type 1 diabetes (T1D) is a chronic, autoimmune, T cell-mediated disease, interventions affecting T cells are expected to modulate the immune cascade and lead to disease remission. We propose that increased CD4(+) CD25(+high) T cell apoptosis, a trait we discovered in recent-onset T1D subjects, reflects T1D partial remission within the first 6 months after diagnosis. Apoptosis of forkhead box P3 (FoxP3)(+) CD4(+) CD25(+high) T cells, in addition to total daily doses of insulin (TDD), blood glucose, HbA1c and age, were measured in 45 subjects with T1D at various times after diagnosis. Sixteen healthy control subjects were also recruited to the study. Higher CD4(+) CD25(+high) T cell apoptosis levels were detected within the first 6 months of diagnosis (odds ratio = 1.39, P = 0.009), after adjustment for age, TDD and HbA1c. A proportional hazards model confirmed that the decline of apoptosis after diagnosis of T1D was related significantly to survival time (hazards ratio = 1.08, P = 0.014), with TDD and age also contributing to survival. During this time there was an inverse relationship between CD4(+) CD25(+high) T cell apoptosis with TDD (r = -0.39, P = 0.008). The CD4(+) CD25(+high) T cell apoptosis levels decline significantly after the first 6 months from diagnosis of T1D and may help in the close monitoring of autoimmunity. In parallel, there is an increase in TDD during this time. We also propose that CD4(+) CD25(+high) T cell apoptosis assay can be used to gauge the efficacy of the several immune tolerance induction protocols, now under way.

Author List

Glisic-Milosavljevic S, Wang T, Koppen M, Kramer J, Ehlenbach S, Waukau J, Jailwala P, Jana S, Alemzadeh R, Ghosh S

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Apoptosis
Cells, Cultured
Diabetes Mellitus, Type 1
Drug Administration Schedule
Female
Follow-Up Studies
Humans
Insulin
Interleukin-2 Receptor alpha Subunit
Male
Remission Induction
T-Lymphocyte Subsets
T-Lymphocytes, Regulatory