Abstract

The reciprocal expansion of Th1 and Th2 subsets is now recognized as a central feature of the immunopathogenesis of several human and experimental diseases. Infection of inbred strains of mice with Leishmania major is the model system for studying the in vivo regulation of protective and non-protective CD4+ subsets and a paradigm for disease that have a genetic basis for susceptibility. Dr Reiner is uniquely positioned to dissect the exact mechanism(s) responsible for the Th1 and Th2 switch in a well- characterized infectious disease model. To facilitate this, he has spent the past year developing an assay that provides a precise method for analysis of in vivo cytokine regulation and successfully generating transgenic mice that express a T cell receptor recognizing a dominant leishmanial epitope. There are three specific aims proposed: 1. To characterize the early immune response to murine leishmaniasis by in vivo analysis of gene expression for various cytokines and effector molecules. 2. To determining the necessary and sufficient conditions governing the preferential expansion of a Th1 and Th2 response to experimental leishmaniasis by in vivo administration and neutralization of critically implicated cytokines in TcR-transgenic mice. 3. To identify the mechanism(s) of genetic susceptibility by in vitro modeling using antigen-presenting and accessory cell populations from resistant and susceptible mice plus transgenic Leishmania-specific T cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI001309-04
Application #
2517126
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1994-09-01
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Reiner, S L; Fowell, D J; Moskowitz, N H et al. (1998) Control of Leishmania major by a monoclonal alpha beta T cell repertoire. J Immunol 160:884-9
Noel, P J; Alegre, M L; Reiner, S L et al. (1998) Impaired negative selection in CD28-deficient mice. Cell Immunol 187:131-8
Swier, K; Brown, D R; Bird, J J et al. (1998) A critical, invariant chain-independent role for H2-M in antigen presentation. J Immunol 160:540-4
Brown, D R; Moskowitz, N H; Killeen, N et al. (1997) A role for CD4 in peripheral T cell differentiation. J Exp Med 186:101-7
Gurunathan, S; Sacks, D L; Brown, D R et al. (1997) Vaccination with DNA encoding the immunodominant LACK parasite antigen confers protective immunity to mice infected with Leishmania major. J Exp Med 186:1137-47
Moskowitz, N H; Brown, D R; Reiner, S L (1997) Efficient immunity against Leishmania major in the absence of interleukin-6. Infect Immun 65:2448-50
Brown, D R; Swier, K; Moskowitz, N H et al. (1997) T helper subset differentiation in the absence of invariant chain. J Exp Med 185:31-41
Brown, D R; Green, J M; Moskowitz, N H et al. (1996) Limited role of CD28-mediated signals in T helper subset differentiation. J Exp Med 184:803-10
Brown, D R; Fowell, D J; Corry, D B et al. (1996) Beta 2-microglobulin-dependent NK1.1+ T cells are not essential for T helper cell 2 immune responses. J Exp Med 184:1295-304
Pearce, E J; Reiner, S L (1995) Induction of Th2 responses in infectious diseases. Curr Opin Immunol 7:497-504

Showing the most recent 10 out of 12 publications