Abstract

The overall goal of this project is to understand how the strength of TCR signalling influences Th2 cell generation. The focus will be on two specific aims: 1) Analysis of the role of CD4 in Th2 differentiation and 2) characterization of IL-4 receptor function during Th differentiation induced by peptides of differing affinity for the T-cell receptor. In vivo studies of immune responses to infectious diseases have indicated that protection against infection is critically dependent on generating the appropriate immune responses and leads to nonhealing lesions and a deficiency in pathogen clearance. Furthermore, many autoimmune diseases are characterized by Th1 destructive responses. Therefore, a critical aspect in addressing inappropriate Th1 or Th2 responses is understanding what factors influence the generation of each type of effector cell responses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI026791-13
Application #
6169999
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Hackett, Charles J
Project Start
1988-07-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
13
Fiscal Year
2000
Total Cost
$353,920
Indirect Cost

  Institution

Name
Yale University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Jackman, Rachael P; Balamuth, Fran; Bottomly, Kim (2007) CTLA-4 differentially regulates the immunological synapse in CD4 T cell subsets. J Immunol 178:5543-51
Balamuth, Fran; Brogdon, Jennifer L; Bottomly, Kim (2004) CD4 raft association and signaling regulate molecular clustering at the immunological synapse site. J Immunol 172:5887-92
Meyer zum Bueschenfelde, Christian O; Unternaehrer, Julia; Mellman, Ira et al. (2004) Regulated recruitment of MHC class II and costimulatory molecules to lipid rafts in dendritic cells. J Immunol 173:6119-24
Jorritsma, Patricia J; Brogdon, Jennifer L; Bottomly, Kim (2003) Role of TCR-induced extracellular signal-regulated kinase activation in the regulation of early IL-4 expression in naive CD4+ T cells. J Immunol 170:2427-34
Eisenbarth, Stephanie C; Piggott, Damani A; Huleatt, James W et al. (2002) Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med 196:1645-51
Brogdon, Jennifer L; Leitenberg, David; Bottomly, Kim (2002) The potency of TCR signaling differentially regulates NFATc/p activity and early IL-4 transcription in naive CD4+ T cells. J Immunol 168:3825-32
Constant, Stephanie L; Brogdon, Jennifer L; Piggott, Damani A et al. (2002) Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ. J Clin Invest 110:1441-8
He, Xin; Janeway Jr, Charles A; Levine, Matthew et al. (2002) Dual receptor T cells extend the immune repertoire for foreign antigens. Nat Immunol 3:127-34
Constant, S L; Lee, K S; Bottomly, K (2000) Site of antigen delivery can influence T cell priming: pulmonary environment promotes preferential Th2-type differentiation. Eur J Immunol 30:840-7
Welte, T; Leitenberg, D; Dittel, B N et al. (1999) The PTK-STAT signaling pathway has essential roles in T-cell activation in response to antigen stimulation. Cold Spring Harb Symp Quant Biol 64:291-302

Showing the most recent 10 out of 26 publications