Involvement of the interleukin 4 pathway in the generation of functional gamma delta T cells from human pro-T cells.
We have used the technique of in situ hybridization to investigate the transcription of genes encoding the CD3 complex and the lymphokine interleukin 4 (IL-4) by human pro-T cells--i.e., cells that phenotypically resemble those T-cell precursors that colonize the thymus during early intrathymic development. CD1-2-3-4-7+8-45+ pro-T cells isolated from postnatal thymi via immunoselection with a panel of specific monoclonal antibodies are already committed to the T-cell lineage because most of them transcribe the genes encoding the delta and epsilon chains of the CD3 complex. About half of such pro-T cells synthesize IL-4 mRNA in the absence of any exogenous stimulation. Upon culture with IL-4, pro-T cells extensively proliferate and differentiate into functionally competent, mature gamma delta T cells expressing a T-cell receptor repertoire similar to that of gamma delta T cells that can be found in postnatal thymus. The IL-4 response of pro-T cells is not mediated by induction of the interleukin 2 (IL-2)-IL-2 receptor pathway and, unlike IL-2-driven T-cell differentiation, does not require the presence of stromal cells. Taken altogether, these findings suggest that an autocrine IL-4-mediated pathway might be implicated in early thymocyte differentiation--namely, in the generation of T cells bearing the gamma delta T-cell receptor.
Bárcena
A
A
Centro de Biología Molecular, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Spain.
Sánchez
M J
MJ
de la Pompa
J L
JL
Toribio
M L
ML
Kroemer
G
G
Martínez-A
C
C
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007223:Infant; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4