T Cell Receptor Complementarity Determining Region 3 Length Analysis Reveals the Absence of a Characteristic Public T Cell Repertoire in Neonatal Tolerance
| Autor: | Stephen S. Wilson, Brian Pedersen, Emanual Michael Maverakis, Anthony Quinn, Eli E. Sercarz, Jonathan T. Beech |
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| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
neonatal tolerance
T cell T-Lymphocytes Immunology Clone (cell biology) Receptors Antigen T-Cell chemical and pharmacologic phenomena Complementarity determining region Lymphocyte Activation Immune tolerance Epitopes Mice Antigen medicine Immune Tolerance Immunology and Allergy Animals Administration Intranasal Cells Cultured Mice Inbred BALB C HEL biology T-cell receptor nasal instillation Isotype Genes T-Cell Receptor medicine.anatomical_structure Animals Newborn biology.protein Original Article Female Muramidase Antibody deletion/anergy T cell repertoire Chickens Spleen |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | All adult BALB/c mice immunized with hen egg white lysozyme (HEL) or its dominant determinant, peptide (p)106–116, mount a T cell response using a “public” Vβ8.2Jβ1.5 T cell clone. Neonatal exposure to tolerance-inducing doses of antigen can drastically diminish responsiveness in the draining lymph nodes but not in the spleens of animals challenged as adults with the cognate antigen. To determine the role of T cell deletion or anergy within the mechanisms of observed neonatal “tolerance,” we treated neonatal BALB/c mice with HEL and directly followed the characteristic public clone using complementarity determining region 3 length T cell repertoire analysis. Our results confirm that despite intraperitoneal injection of neonates with a high dose of HEL emulsified in incomplete Freund's adjuvant, a strong splenic proliferative response to HEL was observed upon recall. However, the adult splenic T cell response of these neonatally treated mice lacked the usual Vβ8.2Jβ1.5 public clone characteristic of HEL-primed BALB/c mice. After challenge with HEL–complete Freund's adjuvant as adults, immunoglobulin (Ig)G2a isotype antibody was drastically reduced, and IgG1 was found to be the predominant anti-HEL IgG isotype expressed, indicating a deviation of cytokine response toward T helper type 2. 5-wk-old mice, nasally instilled with tolerogenic doses of HEL p106–116, also showed significant inhibition of this public T cell expansion. These results demonstrate that during neonatal and adult nasal tolerance induction, deletion/anergy removes the public clone, exposing a response of similar specificity but that is characterized by the T helper type 2 phenotype and a splenic residence. |
| Databáze: | OpenAIRE |
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