T cell receptor complementarity determining region 3 length analysis reveals the absence of a characteristic public T cell repertoire in neonatal tolerance: The response in the "tolerant" mouse within the residual repertoireis quantitatively similar but qualitatively different

All adult BALB/c mice immunized with hen egg white lysozyme (HEL) or its do minant determinant,, peptide (p)106-116, mount a T cell response using a "p ublic" V beta 8.2J beta 1.5 T cell clone. Neonatal exposure to tolerance-in ducing doses of antigen can drastically diminish responsiveness in the drai ning lymph nodes but not in the spleens of animals challenged as adults wit h the cognate antigen. To determine the role of T cell deletion or anergy w ithin 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 analysi s. Our results confirm that despite intraperitoneal injection of neonates w ith a high dose of HEL emulsified in incomplete Freund's adjuvant, a strong splenic proliferative response to HEL was observed upon recall. However, t he adult splenic T cell response of these neonatally treated mice lacked th e usual V beta 8.2J beta 1.5 public clone characteristic of MEL-primed BALB /c mice. After challenge with MEL-complete Freund's adjuvant as adults, imm unoglobulin (Ig)G2a isotype antibody was drastically reduced, and IgG1 was found to be the predominant anti-MEL IgG isotype expressed, indicating a de viation 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 remove s the public clone, exposing a response of similar specificity but that is characterized by the T helper type 2 phenotype and a splenic residence.