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© The Rockefeller University Press, 0022-1007/2000/2/683/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 4, February 21, 2000 683-694


Original Article

Interleukin 4–producing CD4 T Cells Arise from Different Precursors Depending on the Conditions of Antigen Exposure In Vivo

Gilles Foucrasa, Laurent Gapinb, Christiane Coureaua, Jean M. Kanellopoulosb, and Jean-Charles Guérya
a Institut National de la Santé et de la Recherche Médicale (INSERM) U28, Institut Fédératif de Recherche 30, Hôpital Purpan, 31059 Toulouse Cedex, France
b Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, 75724 Paris cedex, France

Correspondence to: Jean-Charles Guéry, INSERM U28, Hôpital Purpan, Place du Dr. Baylac, 31059 Toulouse, France. Tel:33-5-61-77-92-96 Fax:33-5-61-77-92-91 E-mail:Jean-Charles.Guery{at}purpan.inserm.fr.

The precursor origin of T helper (Th) cell subsets in vivo has been difficult to study and remains poorly investigated. We have previously shown that chronic administration of soluble protein antigen induces selective development of antigen-specific CD4 Th2 cells in genetically predisposed mouse strains. 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 lysozyme (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 immunization in complete or incomplete Freund's adjuvant, respectively. Conversely, continuous administration of soluble antigen, which induces strong memory Th2 response, is associated with a dose-dependent reduction of public clone size by a mechanism resembling clonal anergy. Thus, soluble HEL–induced 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 precursor cells.

Key Words: clonal expansion, antigen-specific public repertoire, CD4 T cell subsets, chronic antigen stimulation, clonal anergy


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