Location of Repository

An Opposite Pattern of Selection of a Single T Cell Antigen Receptor in the Thymus and among Intraepithelial Lymphocytes

By Daniel Cruz, Beate C. Sydora, Kristine Hetzel, Gian Yakoub, Mitchell Kronenberg and Hilde Cheroutre


The differentiation of intestinal intraepithelial lymphocytes (IEL) remains controversial, which may be due in part to the phenotypic complexity of these T cells. We have investigated here the development of IEL in mice on the recombination activating gene (RAG)-2−/− background which express a T cell antigen receptor (TCR) transgene specific for an H-Y peptide presented by Db (H-Y/Db × RAG-2− mice). In contrast to the thymus, the small intestine in female H-Y/Db × RAG-2− mice is severely deficient in the number of IEL; TCR transgene+ CD8αα and CD8αβ are virtually absent. This is similar to the number and phenotype of IEL in transgenic mice that do not express the Db class I molecule, and which therefore fail positive selection. Paradoxically, in male mice, the small intestine contains large numbers of TCR+ IEL that express high levels of CD8αα homodimers. The IEL isolated from male mice are functional, as they respond upon TCR cross-linking, although they are not autoreactive to stimulator cells from male mice. We hypothesize that the H-Y/Db TCR fails to undergo selection in IEL of female mice due to the reduced avidity of the TCR for major histocompatibility complex peptide in conjunction with the CD8αα homodimers expressed by many cells in this lineage. By contrast, this reduced TCR/CD8αα avidity may permit positive rather than negative selection of this TCR in male mice. Therefore, the data presented provide conclusive evidence that a TCR which is positively selected in the thymus will not necessarily be selected in IEL, and furthermore, that the expression of a distinct CD8 isoform by IEL may be a critical determinant of the differential pattern of selection of these T cells

Topics: Articles
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2212444
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. A gut-homing, oligoclonal CD41 T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor.
    2. (1990). A new surface antigen on intraepithelial lymphocytes in the intestine.
    3. (1997). Activation and migration of CD8 T cells in the intestinal mucosa.
    4. (1992). An immunological role for the CD8 beta-chain.
    5. (1991). An unusual lineage of a/b T cells that contains autoreactive cells.
    6. (1997). Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD41, CD45RBhigh T cells to SCID recipients.
    7. (1993). Analysis of intraepithelial lymphocytes from major histocompatibility complex (MHC)-deficient mice: no evidence for a role of MHC class II antigens in the positive selection of V delta 41 gamma delta T cells.
    8. (1995). Analysis of the intra-epithelial lymphocyte compartment in SCID mice that received coisogenic CD41 T cells. Evidence that mature post-thymic CD41 T cells can be induced to express CD8 alpha in vivo.
    9. (1996). b2 integrins and ICAM-1 are involved in the establishment of the intestinal mucosal T cell compartment.
    10. (1990). Beta 2-microglobulin deficient mice lack CD4-81 cytolytic T cells.
    11. Beta-chain broadens range of CD8 recognition for MHC class I molecule.
    12. (1996). CD8 enhances formation of stable T-cell receptor/MHC class I molecule complexes.
    13. (1996). CD8b increases CD8 coreceptor function and participation in TCR-ligand binding.
    14. (1995). Co-expression of CD8 alpha in CD41 T cell receptor alpha beta 1 T cells migrating into the murine small intestine epithelial layer.
    15. (1989). Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules.
    16. (1994). Different use of T cell receptor transducing modules in two populations of gut intraepithelial lymphocytes are related to distinct pathways of T cell differentiation.
    17. (1992). Differential function of intestinal intraepithelial lymphocyte subsets.
    18. (1995). Differential requirement of CD28 costimulation for activation of murine CD81 intestinal intraepithelial lymphocyte subsets and lymph node cells.
    19. (1994). Disruption of T lymphocyte positive and negative selection in mice lacking the CD8 beta chain.
    20. (1991). Expression and regulation of beta 7(beta p) integrins on mouse lymphocytes: relevance to the mucosal immune system.
    21. (1993). Expression of two a chains on the surface of T cells in T cell receptor transgenic mice.
    22. (1995). Extrathymic intestinal T-cell development: virtual reality?
    23. (1995). Extrathymic T cell differentiation.
    24. (1998). Generation of intestinal mucosal lymphocytes in SCID mice reconstituted with mature, thymus-derived T cells.
    25. (1996). Immune deviation of 2C transgenic intraepithelial lymphocytes in antigen-bearing hosts.
    26. (1987). Improved procedure for the isolation of functionally active lymphoid cells from the murine intestine.
    27. (1994). Intestinal intraepithelial lymphocytes: the plot thickens.
    28. (1995). Intestinal T cells in CD8 alpha knockout mice and T cell receptor transgenic mice.
    29. (1997). Local hormone networks and intestinal T cell homeostasis.
    30. Mechanism of self-tolerance of g/d T cells in epithelial tissue.
    31. (1992). Most gamma delta T cells develop normally in beta 2-microglobulin-deficient mice.
    32. (1994). Oligoclonal repertoire of the CD8aa and the CD8ab TCR-a/b murine intestinal intraepithelial T lymphocytes: evidence for the random emergence of T cells.
    33. (1994). Phenotypic and functional assessment of intraepithelial lymphocytes bearing a “forbidden” alpha beta TCR.
    34. (1991). Phenotypic complexity of intraepithelial lymphocytes of the small intestine.
    35. (1996). Positive selection is not required for thymic maturation of transgenic gd T cells.
    36. (1988). Positive selection of antigen-specific T cells in thymus by restricting MHC molecules.
    37. (1993). Positive selection of immature alpha beta T cells.
    38. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement.
    39. (1997). Reconstitution of the extrathymic intestinal T cell compartment in the absence of irradiation.
    40. (1994). Reduced thymic maturation but normal effector function of CD81 T cells in CD8b gene-targeted mice.
    41. (1994). Requirement for CD8 beta chain in positive selection of CD8-lineage T cells.
    42. (1992). Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8.
    43. (1992). Selection of intraepithelial lymphocytes with CD8 alpha/alpha co-receptors by self-antigen in the murine gut.
    44. (1994). Selective events in T cell development.
    45. (1993). T cell development in mice lacking the CD3-z/h gene.
    46. (1993). T cell receptor-triggered activation of intraepithelial lymphocytes in vitro.
    47. (1995). T-cell development and selection in the intestinal epithelium.
    48. T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous alpha- and beta-genes.
    49. (1996). TAP-independent selection of CD81 intestinal intraepithelial lymphocytes.
    50. (1992). TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-81 T cells.
    51. (1996). The alpha beta T cell receptor can replace the gamma delta receptor in the development of gamma delta lineage cells.
    52. The generation of mature T cells requires interaction of the alpha beta T-cell receptor with major histocompatibility antigens.
    53. (1994). Thymic and extrathymic origins of gut intraepithelial lymphocyte populations in mice.
    54. (1988). Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells.
    55. Thymus-independent development and negative selection of T cells expressing T cell receptor a/b in the intestinal epithelium: evidence for distinct circulation patterns of gutand thymus-derived T lymphocytes.
    56. (1993). Thymus-independent positive and negative selection of T cells expressing a major histocompatibility complex class I restricted transgenic T cell receptor a/b in the intestinal epithelium.
    57. (1994). Thymus-neuroendocrine interactions in extrathymic T cell development.
    58. (1988). Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4181 thymocytes.
    59. (1991). Two gut intraepithelial CD81 lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation.
    60. (1996). Whence the intestinal intraepithelial lymphocyte?

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.