Limited role of CD28-mediated signals in T helper subset differentiation
| Autor: | C B Thompson, Mark M. Davis, Jonathan Green, N H Moskowitz, S L Reiner, Daniel R. Brown |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Transgene
Cellular differentiation Immunology Priming (immunology) chemical and pharmacologic phenomena Biology Mice Th2 Cells CD28 Antigens medicine Animals Immunology and Allergy Interleukin 4 Mice Inbred BALB C Interferon-gamma production CD28 Cell Differentiation hemic and immune systems T-Lymphocytes Helper-Inducer Articles T helper cell Th1 Cells Cell biology Mice Inbred C57BL medicine.anatomical_structure T cell differentiation Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.184.3.803 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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