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PMID: 9064340 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Limited role of CD28-mediated signals in T helper subset differentiation.

The Journal of experimental medicine ·Vol. 184 ·No. 3 ·1996-09-01 ·Pages 803-10

Brown DR, Green JM, Moskowitz NH, Davis M, Thompson CB, Reiner SL

Abstract

The role of CD28-mediated signals in T helper cell maturation is not fully understood. We tested the requirement for costimulation through CD28 in several systems of CD4+, T cell differentiation. In vivo priming of mice with genetic disruption of CD28 (CD28-/-) yielded normal levels of antigen-specific interferon gamma production but markedly diminished levels of interleukin 4 (IL-4) after in vitro restimulation. In response to the pathogenic microbe, Leishman a major, C57BL6 CD28-/- mice were fully capable of controlling infection and exhibited a normal T helper 1 response. BALB/c CD28-/- mice unexpectedly exhibited normal susceptibility to L. major. BALB/c CD28-/- mice developed high levels of IL-4 mRNA and protein induction in the draining lymph nodes. In addition, susceptibility of BALB/c CD28-/- mice was reversed by neutralization of IL-4 in vivo. We also activated transgenic CD28-bearing T cells from the BALB and C57BL background in vitro in the presence of CTLA4Ig. BALB cells had greater IL-4 producing capacity than C57BL cells in the absence of costimulation. Diverse factors including costimulatory signals, genetic polymorphism, and the nature of the immunogen all influence T helper phenotype commitment, but these results provide evidence that CD28 is not an absolute requirement for generating either Th1 or Th2 responses.

MeSH Terms
Animals CD28 Antigens/physiology Cell Differentiation Mice Mice, Inbred BALB C Mice, Inbred C57BL Signal Transduction T-Lymphocytes, Helper-Inducer/cytology,physiology Th1 Cells/cytology Th2 Cells/cytology
Chemicals
CD28 Antigens
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Brown D R
University of Chicago, Illinois 60637, USA.
Green J M
Moskowitz N H
Davis M
Thompson C B
Reiner S L
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44 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.184.3.803
Published
1996-09-01
Pages
803-10
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192778
Subset
IM
Grants
NIAID NIH HHS · AI-01309 · United States
NIAID NIH HHS · AI-07090 · United States
NIAID NIH HHS · AI-35294 · United States
External Links
PubMed source DOI: 10.1084/jem.184.3.803 PMC Full Text View journal details
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