Thymus and Lymphohemopoietic Cells: Their Role in T Cell Maturation in Selection of T Cells' H‐2‐Restriction‐Specificity and in H‐2 Linked Ir Gene Control

Zinkernagel, Rolf M.

doi:10.1111/j.1600-065x.1978.tb00264.x

Cited by 270 publications

(89 citation statements)

References 117 publications

(91 reference statements)

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“…Previous results obtained in this laboratory and by others (1,3,4) suggest that the H-2 type of the thymus determines the specificity of T cells. Thus, (C57BL × CBA)F1 T cells maturing in a CBA thymus will be restricted to recognizing antigen in association with CBA H-2-coded components.…”

Section: Discussionmentioning

confidence: 53%

“…Thus, once the suppressive mechanism has been induced (which must be very soon after reconstitution of chimeras) it is unable to be abrogated by CY. The suppression observed is most likely mediated by Ts cells rather than by antibody, as it is present in allogeneic chimeras that have been shown by other workers to be immunologically impotent in responses requiring helper cell interactions (1).…”

Section: Discussionmentioning

confidence: 76%

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Suppression of T cells specific for the nonthymic parental H-2 haplotype in thymus-grafted chimeras.

Smith¹,

Miller²

1980

The Journal of Experimental Medicine

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The mechanism of restriction of T-cell specificity by the genotype of the thymus in allogeneic and semiallogeneic chimeras was investigated. Lack of induction of delayed-type hypersensitivity (DTH) directed against antigen in association with the nonthymic parental haplotype in naive cells adoptively transferred into chimeras suggests the existence of an in vivo suppressive mechanism. However, it was not possible to suppress the expression of DTH in sensitized cells transferred into chimeras, or to transfer this suppression to normal naive recipients.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 76%

Suppression of T cells specific for the nonthymic parental H-2 haplotype in thymus-grafted chimeras.

Smith¹,

Miller²

1980

The Journal of Experimental Medicine

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“…Many, but not all (19 -22), experiments indicate that only TCR signaling occurring in response to peptide:MHC molecule ligands displayed by cortical epithelial cells can promote allele-specific positive selection, lineage choice, and export of functional mature T cell maturation of DP thymocytes, whereas MHC molecules on hemopoietic cells are ineffective in this regard (23)(24)(25)(26)(27)(28)(29). MHC ligands on dendritic cells (DC) in particular have been associated with negative, not positive, selection (30), a property most often attributed to a special capacity of these cells to induce thymocyte apoptosis in conjunction with high levels of TCR and possibly CD28 signaling (31)(32)(33)(34).…”

mentioning

confidence: 99%

TCR Signaling for Initiation and Completion of Thymocyte Positive Selection Has Distinct Requirements for Ligand Quality and Presenting Cell Type

Yasutomo

Lucas

Germain

2000

The Journal of Immunology

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Thymocyte selection involves signaling by TCR engaging diverse self-peptide:MHC molecule ligands on various cell types in the cortex and medulla. Here we separately analyze early and late stages of selection to better understand how presenting cell type, ligand quality, and the timing of TCR signaling contribute to intrathymic differentiation. TCR transgenic CD4+CD8+ thymocytes (double positive (DP)) from MHC-deficient mice were stimulated using various presenting cells and ligands. The resulting CD69high cells were isolated and evaluated for maturation in reaggregate cultures with wild-type or MHC molecule-deficient thymic stroma with or without added hemopoietic dendritic cells (DC). Production of CD4+ T cells required TCR signaling in the reaggregates, indicating that transient recognition of self-ligands by DP is inadequate for full differentiation. DC bearing a potent agonist ligand could initiate positive selection, producing activated thymocytes that matured into agonist-responsive T cells in reaggregates lacking the same ligand. DC could also support the TCR signaling necessary for late maturation. These results argue that despite the negative role assigned to DC in past studies, neither the peptide:MHC molecule complexes present on DC nor any other signals provided by these cells stimulate only thymocyte death. These findings also indicate that unique epithelial ligands are not necessary for positive selection. They provide additional insight into the role of ligand quality in selection events and support the concept that following initiation of maturation from the DP state, persistent TCR signaling is characteristic of and perhaps required by T cells.

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“…There is much evidence that, in mice, the ability of virus-specific cytotoxic T lymphocytes to lyse virus-infected target cells is restricted by gene products encoded in the H-2K and H-2D region of the major histocompatibility complex (Doherty, 1980;Zinkernagel, 1978). Similar conclusions have been reached from in vitro studies of virus-specific cytotoxic reactions with human lymphocytes (Sethi et al, 1980).…”

Section: Discussionmentioning

confidence: 81%

In vitro Stimulation of Rabbit T Lymphocytes by Cells Expressing Herpes Simplex Antigens

Kapoor¹,

Ling²,

Nash³

et al. 1982

Journal of General Virology

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Thymus and Lymphohemopoietic Cells: Their Role in T Cell Maturation in Selection of T Cells' H‐2‐Restriction‐Specificity and in H‐2 Linked Ir Gene Control

Cited by 270 publications

References 117 publications

Suppression of T cells specific for the nonthymic parental H-2 haplotype in thymus-grafted chimeras.

Suppression of T cells specific for the nonthymic parental H-2 haplotype in thymus-grafted chimeras.

TCR Signaling for Initiation and Completion of Thymocyte Positive Selection Has Distinct Requirements for Ligand Quality and Presenting Cell Type

In vitro Stimulation of Rabbit T Lymphocytes by Cells Expressing Herpes Simplex Antigens

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