The effect of thymus environment on T cell development and tolerance

Marrack, Philippa; Lo, David; Brinster, Ralph L.; Palmiter, Richard D.; Burkly, Linda C.; Flavell, R.A.; Kappler, John W.

doi:10.1016/0092-8674(88)90578-8

Cited by 308 publications

(147 citation statements)

References 28 publications

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“…Myeloid DCs were grown from bone marrow progenitors, pulsed with the model Ag MCC 87-103 in vitro, and injected into the trachea of unirradiated, semiallogeneic mice, avoiding the problems of interpretation related to earlier semiallogeneic DC adoptive transfer models in which the host animals were immunodeficient and therefore had abnormal lymphoid microarchitecture (40). Our approach required a normal host tolerant of semiallogeneic donor DCs, such as the Tg 36-2 line, expressing the I-E molecule only in the thymus, but not on peripheral APCs (24,36,41). These animals are effectively tolerant of the I-E expressed by the cohort of MCC 87-103 -pulsed DCs.…”

Section: Discussionmentioning

confidence: 99%

“…The 36-2 host has been shown to express Tg I-E only in the thymus, and thus to be incapable of presenting MCC 87-103 peptide (24,36). We also tested whether donor-derived APCs were capable of presenting peptide in the experiment described above by injecting free MCC 87-103 into the lower airways.…”

Section: T Cell Proliferation In Draining Lymph Nodes After Intratracmentioning

confidence: 99%

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Induction of Rapid T Cell Activation, Division, and Recirculation by Intratracheal Injection of Dendritic Cells in a TCR Transgenic Model

Lambrecht

Pauwels

Groth

2000

The Journal of Immunology

167

173

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Dendritic cells (DCs) are thought to be responsible for sensitization to inhaled Ag and induction of adaptive immunity in the lung. The characteristics of T cell activation in the lung were studied after transfer of Ag-pulsed bone marrow-derived DCs into the airways of naive mice. Cell division of Ag-specific T cells in vivo was followed in a carboxyfluorescein diacetate succinimidyl ester-labeled cohort of naive moth cytochrome c-reactive TCR transgenic T cells. Our adoptive transfer system was such that transferred DCs were the only cells expressing the MHC molecule required for presentation of cytochrome c to transgenic T cells. Ag-specific T cell activation and proliferation occurred rapidly in the draining lymph nodes of the lung, but not in nondraining lymph nodes or spleen. No bystander activation of non-Ag-specific T cells was induced. Division of Ag-specific T cells was accompanied by transient expression of CD69, while up-regulation of CD44 increased with each cell division. Divided cells had recirculated to nondraining lymph nodes and spleen by day 4 of the response. In vitro restimulation with specific Ag revealed that T cells were primed to proliferate more strongly and to produce higher amounts of cytokines per cell. These data are consistent with the notion that DCs in the lung are extremely efficient in selecting Ag-reactive T cells from a diverse repertoire. The response is initially localized in the mediastinal lymph nodes, but subsequently spreads systemically. This system should allow us to study the early events leading to sensitization to inhaled Ag.

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Section: Discussionmentioning

confidence: 99%

Section: T Cell Proliferation In Draining Lymph Nodes After Intratracmentioning

confidence: 99%

Induction of Rapid T Cell Activation, Division, and Recirculation by Intratracheal Injection of Dendritic Cells in a TCR Transgenic Model

Lambrecht

Pauwels

Groth

2000

The Journal of Immunology

167

173

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“…(2) Cross tolerance: HLA class II molecules of nonresponders share epitopes with antigen in question. (3) Clonal deletion of T cell repertoire: HLA class II molecules of nonresponders eliminate auto-reactive T cell clones during intrathymic differentiation resulting in "hole" in T cell repertoire (Kisielow et aL, 1988;Marrack et aL, 1988). (4) Suppression: HLA class II molecules of nonresponders generate active suppression.…”

Section: Possible Mechanisms Of Nonresponsiveness Controlled By Hla-cmentioning

confidence: 99%

HLA-linkedImmune suppression genes

Sasazuki

1990

Jap J Human Genet

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SummaryGenetic control of immune response was investigated by family and population analyses in humans. It was first recognized that there are high responders and low or non responders to natural antigens in human population. Family analysis revealed that low responsiveness to streptococcal cell wall antigen (SCW) was inherited as an HLA-linked dominant trait. CD8 + suppressor T ceils existed in low responders and depletion of the CD8 + T ceils from low responders could restore the strong immune response to SCW. Therefore the gene controlling the low response to SCW was designated as an immune suppression gene for SCW.Immune suppression gene for SCW was in strong linkage disequilibrium with particular alleles of HLA-DQ locus. The association between HLA-DQ alleles and low responsiveness mediated by CD8 + suppressor T cell was also observed for schistosomal antigen, Myeobacterium leprae antigen, tetanus toxoid, cryptomeria pollen antigen and hepatitis B virus surface antigen suggesting that low responsiveness to those antigens was also controlled by immune suppression genes. Anti-HLA-DR monoclonal antibodies inhibited the immune response to those antigens of high responders in vitro, but anti-HLA-DQ monoclonal antibodies did not. On the other hand, anti-HLA-DQ monoclonal antibodies restored the immune response in low responders. Therefore, it is suggested that HLA-DR upregulates immune response and that HLA-DQ downregulates it and that HLA-DQ is epistatic to HLA-DR in the regulation of immune response in humans. Furthermore, direct evidence for the differential in immune regulation between HLA-DR and DQ was obtained by analyzing the SCW specific T cell lines from low responders. SCW specific and HLA-DQ restricted CD4+ T cell lines could activate CD8 + suppressor T cells which in turn downregulate SCW specific CD4+ T cells whereas SCW specific and HLA-DR restricted CD4 + T cell lines could not activate CD8 + suppressor T cells. All these observation clearly demonstrated that the HLA-linked

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“…During development, lymphoid stem cells migrate into the thymic rudiment where they differentiate into functionally mature T lymphocytes (1). Among human thymocytes, CD7 + CD2 -CD3 -CD4 -CD8 -(referred hereafter as CD7') cells represent the earliest identifiable step (2)(3)(4) .…”

mentioning

confidence: 99%

Soluble CD23 (Fc epsilon RII) and interleukin 1 synergistically induce early human thymocyte maturation.

Mossalayi

Lecron

Dalloul

et al. 1990

The Journal of Experimental Medicine

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During development, lymphoid stem cells migrate into the thymic rudiment where they differentiate into functionally mature T lymphocytes (1). Among human thymocytes, CD7 + CD2 -CD3 -CD4 -CD8 -(referred hereafter as CD7') cells represent the earliest identifiable step (2-4) . In vitro, these precursors were able to acquire mature T cell antigens (3, 4), but cellular interactions and cytokines necessary for this process are poorly understood. We have previously reported that enriched populations of B lymphocytes from blood produce factors (3, 5) that promote in vitro development of blood-and bone marrow-derived CD7 + CD2 -precursors. Comparing the biochemical characteristics of this B cell-derived activity (3) to known B cell-derived molecules, we found its striking homology to soluble CD23 (sCD23 ; sFcERII) (6, 7) . Using recombinant sCD23 (rsCD23) (7), we then assayed the effect of this molecule alone or with rIL-1 and/or rIL-2 on purified CD7 + thymic precursors . Our results provide direct evidence that sCD23 and rIL-1 synergistically induce CD7 + prothymocytes maturation into CD2'CD3'TCRa//3+ CD4 + and/or CD8 + cells that respond to CD2 triggering and rIL-2.

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The effect of thymus environment on T cell development and tolerance

Cited by 308 publications

References 28 publications

Induction of Rapid T Cell Activation, Division, and Recirculation by Intratracheal Injection of Dendritic Cells in a TCR Transgenic Model

Induction of Rapid T Cell Activation, Division, and Recirculation by Intratracheal Injection of Dendritic Cells in a TCR Transgenic Model

HLA-linkedImmune suppression genes

Soluble CD23 (Fc epsilon RII) and interleukin 1 synergistically induce early human thymocyte maturation.

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