A common precursor for CD4+ T cells producing IL-2 or IL-4.
To investigate whether CD4+ T cells are predetermined to produce a given pattern of lymphokines, we have used a culture system that allows the controlled induction of either IL-2- or IL-4-producing CD4+ T cells. Single, freshly isolated murine CD4+ T cells were activated with Con A, rIL-2, and APC; the developing clones were split and then cultured for an additional 14 days with either rIL-2 alone or with rIL-2 and anti-CD3 stimulation. Subclones expanded in the presence of rIL-2 alone produced predominantly IL-2, although subclones derived from the same precursor and expanded in the presence of rIL-2 and a mitogenic antibody to CD3 released predominantly IL-4. Subclones expanded for 2 wk in the presence of rIL-2 plus a mitogenic mAb to CD3 released up to 60 times more IL-4 but only 1/90 the amount of IL-2 released by subclones derived from the same precursor cell and expanded with rIL-2. Both phenotypes can be derived from IL-2-producing precursor cells. These results demonstrate that IL-2-producing clones can be derived from the same cells as IL-4-producing clones and are most consistent with the view that the IL-2-producing Th1 or the IL-4-producing Th2 phenotype of a T cell clone is acquired during T cell differentiation and is not secondary to the expansion of distinct subpopulations that are predetermined to produce a specific cytokine pattern.
Department of Dermatology, Hôpital Cantonal Universitaire de Geneve, Switzerland.
M
M
Röcken
J H
JH
Saurat
C
C
Hauser
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4