The roles of Cabin1 and Left1 in T cell development

Cabinl binds calcineurin and myocyte enhancer factor 2 (MEF2) through the C-terminal region. In cell lines, these interactions inhibit calcineurin activity following TCR signaling and transcriptional activation of Nur77 by MEF2. The role of these interactions in vivo was investigated using a mutant mouse strain that expresses a truncated Cabin 1 lacking the C-terminal calcineurin and MEF2 binding domains. Although mutant mice exhibited normal lymphocyte development and thymocyte apoptosis, they had elevated levels of serum IgG 1, IgG2b and IgE and produced more IgG1 and IgG2b in response to a T-dependent antigen. The increased antibody production is apparently not due to changes in immunoglobulin class switching as B cells from mutant mice switched to IgG 1 at the same frequency as wildtype B cells in vitro in the presence of IL-4. However, in response to anti-CD3 stimulation, mutant T cells expressed significantly higher levels of IL-2, IL-4, IL-9, IL-13, and IFN-y. Thus, the calcineurin and MEF2 binding domain of Cabin 1 is dispensable for thymocyte development and apoptosis, but is required for proper regulation of T cell cytokine expression and Th2 antibody responses. In our analysis of gene expression in memory CD8+ T cells, we identified a member of the membrane spanning 4A gene family, MS4a4b, which we named Leftl. It was also found to be expressed in Thl, but not Th2 cells. To examine the role of Leftl in T cell development, we created transgenic mice which express Leftl in T cells. These mice revealed a role for Leftl at multiple stages of T cell development.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2001

Author dc:creator

• Esau, Christine C. (Christine Carol), 1972-

Advisor dc:contributor.advisor

• Jianzhu Chen.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8208

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8208