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Most IL-4-Producing Thymocytes of Adult Mice Originate from Fetal Precursors ¹

Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Institut Pasteur, Paris, France

Thy-1^dull T cells constitute a distinct adult T cell subset characterized by the expression of a TCR composed of V1C4 and V6C chains with limited junctional sequence diversity. However, several features of the expressed Thy-1^dull TCR- genes, in particular the absence or minimal presence of N region diversity and the almost invariable D2-J1 junction, are typical of rearrangements often found in the fetal thymus. In this study, we have investigated the origin of these cells. Few Thy-1^dull thymocytes developed in syngeneic radiation adult chimeras, regardless of whether the recipient mice were given adult bone marrow or fetal liver cells as a source of hemopoietic precursors. In contrast, normal numbers of Thy-1^dull T cells developed in fetal thymi grafted into adult syngeneic recipients. Interestingly, the majority of Thy-1^dull thymocytes present in the grafts were of graft origin, even when most conventional and thymocytes in the grafted thymi originated from T cell precursors of recipient origin. Single-cell PCR analyses of the nonselected TCR- rearrangements present in adult Thy-1^dull thymocytes revealed that more than one-half of these cells represent the progenies of a limited number of clones that greatly expanded possibly during the first weeks of life. Finally, the second TCR- allele of a large number of Thy-1^dull T cells contained incomplete TCR- rearrangements, thus providing an explanation for the adult-type rearrangements previously found among nonfunctional V(D)J rearrangements present in Thy-1^dull thymocytes.

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