Interleukin 4-producing CD4 T cells arise from different precursors depending on the conditions of antigen exposure in vivo

The precursor origin of T helper (Th) cell subsets in vivo has been difficu lt to study and remains poorly investigated. We have previously shown that chronic administration of soluble protein antigen induces selective develop ment of antigen-specific CD4 Th2. cells in genetically predisposed mouse st rains. To analyze the origin of effector T cells in this model, we designed a competitive polymerase chain reaction-based approach to track public BV- J rearrangement expressed by CD4 T cells specific for hen egg white lysozym e (HEL) in BALB/c mice. We show that public T cell clones are predominantly associated with type 1 or 2 effector Th cells recovered after primary immu nization in complete or incomplete Freund's adjuvant, respectively. Convers ely, continuous administration of soluble antigen, which induces strong mem ory Th2 response, is associated with a dose-dependent reduction of public c lone size by a mechanism resembling clonal anergy. Thus, soluble MEL-induce d Th2 cells do not express the public complementarity determining region 3 motifs characteristic of immunogenic challenge in the presence of adjuvant. These results demonstrate that there are multiple pathways of induction of Th2 responses depending on the condition of antigen exposure in vivo, i.e. , clonal immune deviation versus recruitment of a different pool of precurs or cells.