| First Author | Kweon MN | Year | 1999 |
| Journal | J Immunol | Volume | 162 |
| Issue | 4 | Pages | 1904-9 |
| PubMed ID | 9973457 | Mgi Jnum | J:112042 |
| Mgi Id | MGI:3655417 | Doi | 10.4049/jimmunol.162.4.1904 |
| Citation | Kweon MN, et al. (1999) Mucosally induced systemic T cell unresponsiveness to ovalbumin requires CD40 ligand-CD40 interactions. J Immunol 162(4):1904-9 |
| abstractText | CD40 ligand (CD40L) gene-disrupted (CD40L-/-) mice were employed to examine the role of costimulatory signals via CD40L-CD40 interactions in mucosally induced tolerance. CD40L-/- and control (CD40L+/+) mice of the same C57BL/6 x 129/J background were immunized orally with 25 mg of OVA before systemic challenge with OVA in CFA. While CD40L+/+ mice showed reductions in Ag-specific T cell responses including delayed-type hypersensitivity (DTH) and proliferative responses, CD40L-/- mice underwent normal T cell responses. Further, cytokine analysis of splenic CD4+ T cells showed that both Th1-type (e.g., IFN-gamma and IL-2) and Th2-type (e.g., IL-4, IL-5, IL-6, and IL-10) responses were maintained in CD40L-/- mice orally immunized with OVA, whereas these cytokine responses in CD40L+/+ mice were significantly reduced. In addition, splenic CD4+ T cells from CD40L-/- mice orally immunized with OVA provided B cell help in Ag-specific Ab-forming cells when the cells were cultured with naive B cells in the presence of Ag and CD40L-transfected cell lines. In contrast, an identical culture condition containing splenic CD4+ T cells from orally tolerized CD40L+/+ mice did not exhibit helper activity. Taken together, these findings indicate that CD40L and CD40 interactions are essential for the induction of systemic T cell unresponsiveness to orally administered Ag. |
