Reduced expression of decay-accelerating factor 1 on CD4+ T cells in murine systemic autoimmune disease.

Abstract

OBJECTIVE:

Deficiency of decay-accelerating factor 1 (termed Daf1 in mice) has been shown to exacerbate autoimmunity, and recent studies have suggested that this may be explained by Daf1 acting as a regulator of T cell immunity. The aim of this study was to determine whether Daf1 expression on T cells is modulated during development of autoimmunity in mice.

METHODS:

To test this hypothesis, we examined Daf1 levels in NZB, DBA/2, and B10.S mice before and after induction of murine mercury-induced autoimmunity (mHgIA). Daf1 was measured by real-time polymerase chain reaction and flow cytometry, and levels of Daf1 were correlated with markers of lymphocyte activation and cytokine production.

RESULTS:

Autoimmune-prone NZB mice had low endogenous levels of Daf1 irrespective of the induction of mHgIA. Induction of autoimmunity reduced Daf1 expression in mHgIA-sensitive B10.S mice, particularly on activated/memory (CD44(high)) CD4+ T cells that accumulate as a result of exposure to mercury. Murine mercury-induced autoimmunity-resistant DBA/2 mice, which fail to accumulate CD44(high) T cells, showed no change in Daf1 expression. Modulation of Daf1 expression was found to require CD4+ T cell costimulation, since B10.S mice deficient in CD28 were unable to down-regulate Daf1 or accumulate activated/memory CD4+ T cells. In B10.S mice exposed to mercury, the production of interleukin-4 (IL-4), but not that of IL-2 or interferon-gamma, in the spleen was associated with CD44(high),Daf1(low),CD4+ T cells.

CONCLUSION:

These findings demonstrate that reduction of Daf1 expression is closely associated with CD4+ T cell activation and the accumulation of CD44(high)(activated/memory),CD4+ T cells in both spontaneous and induced systemic autoimmune disease.

• Authors: David M Cauvi, Gabrielle Cauvi, K Michael Pollard
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 56 Issue 6 Pg. 1934-44 (Jun 2007) ISSN: 0004-3591 [Print] United States
• PMID: 17530719 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CD55 Antigens
• Hyaluronan Receptors
• RNA, Messenger
• decay-accelerating factor 1, mouse
• Interleukin-4
• Mercury

Topics

• Animals
• Autoimmune Diseases (chemically induced, genetics, metabolism)
• Autoimmunity (genetics)
• B-Lymphocytes (metabolism, pathology)
• CD4-Positive T-Lymphocytes (metabolism, pathology)
• CD55 Antigens (genetics, metabolism)
• Gene Expression Regulation
• Hyaluronan Receptors (genetics, metabolism)
• Interleukin-4 (genetics, metabolism)
• Mercury
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Mice, Inbred NZB
• Mice, Knockout
• RNA, Messenger (genetics, metabolism)