Positive selection of CD4+ and CD8+ T cells

Current Opinion in Immunology

Volumn 8, Issue 2, 1996, Pages 225-232

  Guidos, Cynthia J ^a  

^a HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN;

LYMPHOCYTE DIFFERENTIATION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

EID: 0029951040     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(96)80061-6     Document Type: Article

References (51)

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6. + thymocytes as post-selection intermediates leading to mature T cells. J Exp Med 1991, 173:323-332.
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9. + stage during positive selection and promotes thymocyte differentiation at several control points. Immunity 1994, 1:197-205.
10. + mature thymocytes require different post-selection processing for final development. J Immunol 1993, 151:1273-1279.
11. + thymocytes. J Exp Med 1995, 181:193-202. This study showed that in vitro TCR cross-linking of DP thymocytes stimulates several early outcomes of positive selection, including increased synthesis of TCRα protein and elevated CD5 expression. Down regulation of CD4 and CD8 was also induced, but in the absence of apoptosis.
12. + cell lines in response to TCR engagement. J Immunol 1995, 154:5011-5022. The authors describe that clonal DP thymic lymphoma cell lines (similar to fresh ex vivo DP thymocytes) respond to in vitro TCR engagement by undergoing a spectrum of maturation events known to be early outcomes of positive selection in vivo.
13. Kouskoff V, Vonesh J-L, Benoist C, Mathis D: The influence of positive selection on RAG expression in thymocytes. Eur J Immunol 1995, 25:54-58. This study compares RAG-1 expression in positively selecting versus neutral strains by in situ hybridization of thymus sections and RT-PCR of sorted cells. The results show that downregulation of RAG-1 expression begins in cortical DP thymocytes but is not completed until the mature, SP stage.
14. hi DP thymocytes was seen only after intrathymic transfer into a positively selecting host, suggesting that continual TCR engagements are required to induce the full spectrum of differentiation events associated with positive selection.
15. + DP thymocytes to complete differentiation. In addition, these investigators present evidence that early and late stages of positive selection may use different signaling pathways.
16. int thymocytes predominantly give rise to CD8 SP thymocytes in vitro. Thus, partial downregulation of CD8 is a poor indicator of commitment to the CD4 lineage.
17. Guidos CJ, Danska JS, Fathman CG, Weissman IL: T cell receptor-mediated negative selection of autoreactive T lymphocyte precursors occurs after commitment to the CD4 or CD8 lineages. J Exp Med 1990, 172:835-845.
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20. + thymocytes: selection rather than instruction? Science 1993, 261:911-915.
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22. Kersh GJ, Hedrick SM: Role of TCR specificity in CD4 versus CD8 lineage commitment. J Immunol 1995, 154:1057-1068. Phenotypic analyses of thymocytes from class I MHC- or class II MHC-deficient mice and TCR transgenic mice suggest that TCR specificity plays a crucial role in the development of co-receptor transitional thymocytes expressing high levels of CD69 or CD5.
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25. + cells.
26. lo thymocytes require further intrathymic development before they can become functionally immunocompetent.
27. int phenotype of these cells does not reflect commitment to the CD4 lineage.
28. ••], but also suggest that an instructional mechanism governs commitment to the CD8 lineage, whereas CD4 T cells develop stochastically.
29. + thymocytes are not observed in class I MHC-deficient mice.
30. + T cells, but they express only low levels of CD8 and are non-functional. This result bears on the interpretation of similar experiments that support the differential-avidity model of thymocyte development.
31. Chervonsky AV, Golovkina TV, Ross SR, Janeway CA Jr: Differences in the avidity of TCR interactions with a superantigenic ligand affect negative selection but do not allow positive selection. J Immunol 1995, 155:5115-5123. Low concentrations of endogenous superantigens mediate negative selection or have no effect on selection of superantigen-specific TCR, but do not result in positive selection. This result conflicts with predictions based on the differential avidity model, and is interpreted to suggest that distinct ligands drive positive and negative selection.
32. + T cells to TAP-1 deficient mice, suggesting that selection can occur on empty class I MHC molecules, or be mediated by TAP-independenl peptide-MHC complexes.
33. 2m-dependent but TAP-independent. This suggests that, in contrast to classical MHC class Ia molecules, biosynthesis of CD1 and other class Ib molecules may involve association with a TAP-independent pool of cytosolic peptides, or may be completely peptide-independent.
34. + T cells is shown to recognize the class Ib MHC molecule CD1, which is considerably less polymorphic than conventional class Ia MHC molecules and is encoded outside the MHC locus.
35. + T cells.
36. + T cells specific for a related hemoglobin molecule. The results suggest that presentation of endogenous peptides profoundly shapes the CD4 T-cell repertoire.
37. + T cells.
38. + T cells, suggesting that li is directly involved in positive selection.
39. Denzin LK, Cresswell P: HLA-DM induces CLIP dissociation from MHC class II αβ dimers and facilitates peptide loading. Cell 1995, 82:155-165. Biochemical studies reveal that the human class II MHC molecule, HLA-DM, facilitates peptide loading of other class II molecules by inducing dissociation of the invariant chain-derived CLIP peptide which is acquired during class II biosynthesis.
40. Tarakhovsky A, Kanner SB, Hombach J, Ledbetter JA, Müller W, Killeen N, Rajewsky K: A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 1995, 269:535-537. Thymocytes from CD5-deficient mice are shown to be hyper-responsive to TCR stimulation. The effect of CD5 deficiency on selection in vivo varies with TCR specificity, suggesting that CD5 can modulate signaling during positive or negative selection.
41. Chan A, Kadlecek T, Elder M, Filipovich A, Kuo W-L, Iwashima M, Parslow M, Weiss A: ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science 1994, 264:1599-1601.
42. Elder M, Lin D, Clever J, Chan A, Hope T, Weiss A, Parslow T: Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science 1994, 264:1596-1599.
43. + thymic selection in humans lacking ZAP-70 kinase. Cell 1994, 76:947-958.
44. + T cells. Previous studies of human patients with defective ZAP-70 had suggested a selective requirement for this kinase in CD8 T-cell development.
45. + thymocytes. Nature 1995, 374:474-477. Absence of the Vav signaling molecule is shown to severely impair TCR signaling in DP thymocytes and constrain early outcomes of positive selection in vivo. Downregulation of CD4 and CD8, however, appears to be unaffected, as evidenced by the appearance of co-receptor transitional thymocytes. These data suggest that distinct signaling mechanisms regulate the multiple outcomes of positive selection.
46. Crump AL, Grusby MJ, Glimcher LH, Cantor H: Thymocyte development in major histocompatibility complex-deficient mice: evidence for stochastic commitment to the CD4 and CD8 lineages. Proc Natl Acad Sci USA 1993, 90:10739-10743.
47. + thymocytes in vitro. J Immunol 1995, 154:3636-3643. The calcineurin inhibitor cyclosporin A is used to distinguish signaling pathways used for positive and negative selection as thymocytes mature in the reaggregate culture system.
48. Wang C-R, Hashimoto K, Kubo S, Yokochi T, Kubo M, Suzuki M, Suzuki K, Tada T, Nakayama T: T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but negative selection. J Exp Med 1995, 181:927-941. The calcineurin inhibitor, FK506, blocks positive selection in vivo, and impairs TCP-induced differentiation of DP thymoctyes in vitro. In contrast, negative selection is unperturbed by this treatment, suggesting that different signaling pathways regulate these two aspects of thymocyte development.
49. ras transgene selectively blocks positive selection, suggesting that this process is biochemcially distinguishable from negative selection.
50. ••], suggest that quantitatively or qualitatively distinct signaling mechanisms regulate positive and negative selection.
51. + thymocytes in vitro induces early aspects of positive selection, but not apoptosis. J Immunol 1996, in press.