Resource Logo

Alteration of interleukin 4 production results in the inhibition of T helper type 2 cell-dominated inflammatory bowel disease in T cell receptor alpha chain-deficient mice.


J Exp Med. 1999 Sep 6;190(5):607-15. Unique Identifier : AIDSLINE

T cell receptor alpha chain-deficient (TCR-alpha(-/-)) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4(+)TCR-betabeta (CD4(+)betabeta) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4(+)betabeta T cells, we treated TCR-alpha(-/-) mice with anti-IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-alpha(-/-) mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti-IL-4 mAb-treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab-treated mice. Although TCR-alpha(-/-) mice treated with either specific or mock Ab developed CD4(+)betabeta T cells, only those treated with anti-IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon gamma-specific expression. These findings suggest that IL-4-producing Th2-type CD4(+)betabeta T cells play a major immunopathological role in the induction of IBD in TCR-alpha(-/-) mice, a role that anti-IL-4 mAb inhibits by causing Th2-type CD4(+)betabeta T cells to shift to the Th1 type.

JOURNAL ARTICLE Animal Antibodies, Monoclonal/PHARMACOLOGY Cytokines/BIOSYNTHESIS/GENETICS CD4-Positive T-Lymphocytes/IMMUNOLOGY Immunity, Mucosal Immunoglobulins/BIOSYNTHESIS In Vitro Inflammatory Bowel Diseases/ETIOLOGY/*IMMUNOLOGY/*PREVENTION & CONTROL Interferon Type II/BIOSYNTHESIS/GENETICS Interleukin-4/ANTAGONISTS & INHIB/*BIOSYNTHESIS/GENETICS Interleukin-6/BIOSYNTHESIS/GENETICS Intestinal Mucosa/IMMUNOLOGY/PATHOLOGY Mice Mice, Inbred C57BL Mice, Knockout Receptors, Antigen, T-Cell, alpha-beta/*DEFICIENCY/GENETICS RNA, Messenger/GENETICS/METABOLISM Support, Non-U.S. Gov't Th1 Cells/IMMUNOLOGY Th2 Cells/*IMMUNOLOGY


Information in this article was accurate in December 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.