Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 107K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maverakis, E. Articles by Sercarz, E. E. Search for Related Content PubMed PubMed Citation Articles by Maverakis, E. Articles by Sercarz, E. E. Pubmed/NCBI databases Substance via MeSH Social Bookmarking                            What's this?

Original Article

Emanual Maverakis^a, Jonathan T. Beech^a, Stephen S. Wilson^a, Anthony Quinn^a, Brian Pedersen^a, and Eli E. Sercarz^a

^a La Jolla Institute for Allergy and Immunology, San Diego, California 92121
La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121.619-558-3525619-678-4559

eli{at}liai.org

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.

Key Words: neonatal tolerance • deletion/anergy • nasal instillation • HEL • T cell repertoire

Abbreviations used in this paper: HEL, hen egg white lysozyme; RIS, relative intensity of signal.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS