Signals through CD8 or CD4 can induce commitment to the CD4 lineage in the thymus

European Journal of Immunology
U BommhardtR Zamoyska

Abstract

Differentiation of thymocytes into mature single-positive T cells is an ordered process involving sequential interactions between T cell receptor (TCR), co-receptors (CD4 or CD8) and their appropriate major histocompatibility complex-encoded ligands. Precisely how these receptor/co-receptor engagements determine lineage commitment is still controversial, but recently it has been suggested that quantitative differences in the signal transmitted by co-ligation of CD4 versus CD8 with TCR might provide the discriminating signal. We examine this hypothesis, using bispecific F(ab')2 antibodies to mimic TCR/ co-receptor engagement during thymocyte differentiation. These bispecific antibodies lack Fc and can engage surface molecules without extensive cross-linking or targeting to Fc receptor-bearing cells. We show that TCR/CD3 co-ligation with CD4 induces efficient differentiation of mature CD4 lineage cells, irrespective of their TCR specificity. Interestingly, TCR/CD3 co-ligation with CD8 also induces maturation of CD4 T cells, although less efficiently, but not of CD8 T cells. Thus, although the signals delivered by co-ligation of TCR and CD8 appear weaker than from co-ligation of TCR and CD4, the outcome from either engagement is t...Continue Reading

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Citations

Oct 3, 1999·European Journal of Immunology·S ChanD Mathis
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Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M A BassonR Zamoyska
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shin-Young NaUrsula Bommhardt
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Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·U BommhardtT Hünig

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