Transgenic expression of CTLA-4 controls lymphoproliferation in IL-2-deficient mice
- Authors
- Hwang, KW; Sweatt, WB; Mashayekhi, M; Palucki, DA; Sattart, H; Chuang, E; Alegre, ML
- Issue Date
- 1-Nov-2004
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Citation
- JOURNAL OF IMMUNOLOGY, v.173, no.9, pp 5415 - 5424
- Pages
- 10
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Volume
- 173
- Number
- 9
- Start Page
- 5415
- End Page
- 5424
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24740
- DOI
- 10.4049/jimmunol.173.9.5415
- ISSN
- 0022-1767
1550-6606
- Abstract
- IL-2-deficient mice develop a lymphoproliferative and autoimmune disease characterized by autoimmune hemolytic anemia (AHA) and inflammatory bowel disease. We have previously reported that IL-2 is necessary for optimal up-regulation of CTLA-4, an inducible negative regulator of T cell activation. In this study, we have tested the hypothesis that reduced expression of CTLA-4 in IL-2-deficient T cells contributes to the pathogenesis of disease in IL-2-deficient, mice. Expression of CTLA-4 as a transgene completely prevented lymphoaccumulation and AHA in IL-2-deficient mice. The normalization of T cell numbers was due to inhibition of expansion of conventional CD4(+)CD25(-) T cells rather than to rescue of the numbers or function of CD4(+)CD25(+) regulatory T cells, suggesting that CTLA-4 expression on conventional T cells plays a role in maintaining normal T cell homeostasis. In addition, the inhibitory effect of the CTLA-4 transgene on T cell expansion was at least in part independent of CD28 expression. Our results suggest that deficient CTLA-4 expression on conventional T cells contributes to the pathophysiology of the lymphoproliferative disease and AHA in IL-2-deficient mice. Thus, restoring CTLA-4 expression in T cells may be an attractive strategy to control clinical autoimmune diseases in which CTLA-4 expression is reduced.
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