The thymus in “bare lymphocyte” syndrome: Significance of expression of major histocompatibility complex antigens on thymic epithelial cells in intrathymic T-cell maturation

Schuurman, Henk‐Jan; Wijngaert, Frank P. van de; Huber, J.; Schuurman, R. K. B.; Zegers, B. J. M.; Roord, John J.; Kater, L.

doi:10.1016/0198-8859(85)90014-x

Cited by 38 publications

(11 citation statements)

References 22 publications

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“…This indicates that CIITA-independent MHC II expression could play a role in the maturation of CD4 1 T cells in the thymus. Furthermore, the biopsy specimen of the thymus from a BLS patient demonstrated the decreased MHC II expression pattern, which is quite similar to that from CIITA-deficient mice [37]. Consistent with this, there was a small but a significant number of mature CD4 1 T cell lymphocytes even in thymomas with severely impaired CIITA expression.…”

Section: Discussionsupporting

confidence: 69%

Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-γ)

Kadota

Okumura

Miyoshi

et al. 2000

Clinical and Experimental Immunology

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SUMMARYThymoma is known to contain CD4 1 CD8 1 T cells, indicating that neoplastic epithelial cells of thymoma have a function as thymic cortical epithelium. However, it has been shown that there is an impairment of CD4 1 T cell development in thymoma and that IFN-g-induced HLA-DR expression on cultured thymic epithelial cells (TEC) derived from thymoma is decreased when compared with the normal thymus. MHC class II transactivator (CIITA) is known to play a critical role in IFN-g-induced MHC II expression. In this study, we attempted to elucidate whether CIITA is responsible for the impaired up-regulation of MHC II molecules in response to IFN-g in thymoma TEC. A quantitative reverse transriptase-polymerase chain reaction examination revealed that the induced level of CIITA was significantly lower in thymoma TEC than in normal TEC. The induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated with CIITA expression. The proportion of CD3 1 cells in the CD4 1 CD8 2 subset in thymoma was also correlated with CIITA expression. A gel mobility shift assay however, revealed translocation of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC to a level similar to normal TEC in response to IFN-g. These results indicate that impaired up-regulation of HLA-DR in response to IFN-g results from insufficient induction of CIITA, but not from the signal from IFN-g receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired induction of CIITA may affect CD4 1 T cell development in thymoma.

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Section: Discussionsupporting

confidence: 69%

Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-γ)

Kadota

Okumura

Miyoshi

et al. 2000

Clinical and Experimental Immunology

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“…In view of the mild clinical phenotype of the twin brothers investigated, the present findings reconfirm the important role of dendritic cells for the immune system, and illustrate how little MHC class II expression might be needed to mount a functional cellular immune response in vivo . In other patients with MHC class II deficiency, dendritic cells have been reported to lack MHC class II molecules (Schuurman et al , 1985; Griscelli et al , 1993; Emile et al , 1997). These patients develop severe clinical symptomatology within their first year of life, such as recurrent diarrhoea, failure to thrive and life‐threatening infections, that invariably persist during follow‐up unless curative treatment in the form of bone marrow transplantation is provided (Klein et al , 1993).…”

Section: Discussionmentioning

confidence: 99%

Residual expression of functional MHC class II molecules in twin brothers with MHC class II deficiency is cell type specific

Wolf¹,

Thon²,

Gulle³

et al. 2001

Br J Haematol

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Summary. We examined major histocompatibility complex (MHC) class II expression in B cells, peripheral blood monocytes, activated T cells, epidermal Langerhans cells, monocyte-derived dendritic cells, dermal microvascular endothelial cells (DMEC) and fibroblasts of twin brothers with MHC class II deficiency. Although residual human leucocyte antigen (HLA)-DR expression was found on a subpopulation of epidermal Langerhans cells and a subset of peripheral blood monocyte-derived dendritic cells, the patients' B cells, monocytes and activated T cells were HLA-DR negative. After treatment with interferon-g (IFNg), the patients' DMEC expressed HLA-DR but not -DP and -DQ at the protein and mRNA level, whereas IFN-g failed to induce HLA-DR expression on dermal fibroblasts. The patients' monocyte-derived dendritic cells were capable of processing and presenting tetanus toxoid to autologous T cells, and patient-derived DMEC induced the proliferation of allogeneic CD41 T cells in an MHC class II-restricted fashion, indicating that the observed residual MHC class II surface expression was functional. The findings reported show that the defect encountered in these patients is not necessarily expressed to the same extent in different cell lineages, which is relevant for the understanding of the patients' phenotype and also illustrates that only small amounts of MHC class II are needed to mount a functional cellular immune response in vivo.

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“…The genes encoding MHC class II are intact, yet there is usually no expression of the gene products. In a few cases, decreased expression of MHC class II in the thymus has been demonstrated [1,2], The defect, which cannot be corrected by interferon-gamma (IFN-->) [3], has been shown to occur at the transcriptional level [4] and is apparently heterogeneous. A study employing fusion experiments between B lymphoblastoid cell lines derived from various MHC class Ildeficient patients demonstrated that genetic defects in three to four transactivating factors can lead to failure to transcribe and express MHC class II genes [5].…”

Section: Introdlctionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

T cell differentiation and generation of the antigen-specific T cell repertoire in man: observations in MHC class II deficiency

Mannhalter

Wolf

Hauber

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThe circulating T cell pool of an MHC class TI-deficient patient was shown to lack the MHC class IT-specific T cell functions. This was demonstrated by the absence of MHC class II-specific alloreactive T cells and a substantially decreased number of circulating CD4' lymphocytes. The patient's T cells did respond to an allostimulus, although the restriction pattern of this reaction remains speculative. The function and distribution of peripheral T cell subsets from the patient resemble findings in MHC class TI-deficient mice, which also lack interaction of T cell precursors with MHC class TI-bearing accessory cells during thymic differentiation. Our data support the concept that T cell differentiation in humans is similar, and that the human MHC-restricted T cell repertoire depends on prior interaction of T cell precursors with self MHC.

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The thymus in “bare lymphocyte” syndrome: Significance of expression of major histocompatibility complex antigens on thymic epithelial cells in intrathymic T-cell maturation

Cited by 38 publications

References 22 publications

Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-γ)

Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-γ)

Residual expression of functional MHC class II molecules in twin brothers with MHC class II deficiency is cell type specific

T cell differentiation and generation of the antigen-specific T cell repertoire in man: observations in MHC class II deficiency

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