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G Thoenes

Publications and source records attributed to G Thoenes.

8 recordsLinked to original sources
PubMed1992

Structural analysis of low TCR-CD3 complex expression in T cells of an immunodeficient patient.

Normal membrane expression of the T cell receptor (TCR) depends on the coordinated synthesis and assembly of all seven proteins composing the complex, i.e. the TCR alpha and beta chains, the CD3 gamma, delta, and epsilon chains, and the zeta-zeta or zeta-eta dimer. In an experimental TCR membrane-defective T cell variant (Sussman, J. L., Bonifacino, J. S., Lippincott-Schwartz, J., Weissman, A. M., Saito, T., Klausner, R. D., and Ashwell, J. D. (1988) Cell 52, 85-95) and in two siblings whose lymphocytes express only a low level of the TCR/CD3 complex (Alarcon, B., Berkhout, B., Breitmeyer, J., and Terhorst, C. (1988) N. Engl. J. Med. 319, 1203-1208), a defect in zeta chain synthesis and/or assembly was thought to account for the defective membrane synthesis of the whole complex. We report on another immunodeficient patient whose T lymphocytes express the T cell receptor at one-tenth of normal fluorescence intensity and are not triggered to proliferate in vitro by anti-CD3 or anti-CD2 antibodies. Biochemical analysis of the patient's surface-iodinated peripheral blood lymphocytes failed to detect TCR alpha and beta, or CD3 gamma, delta, and epsilon proteins but revealed the presence of the zeta homodimer (probably as a result of the high proportion of natural killer cells). In the cytoplasm, TCR alpha and beta proteins and the zeta chain were detected, but, using monoclonal anti-CD3 antibodies, the CD3 gamma, delta, and epsilon chains were not. In addition, the CD3 epsilon chain was not detected with polyclonal antiserum in a very sensitive Western blotting detection system. The zeta chain was shown to be synthesized by the patient's T and natural killer cells. Northern blot analysis revealed normal levels of normal-size TCR beta and CD3 gamma, delta gene-specific mRNAs and decreased levels of TCR alpha mARN; CD3 epsilon gene transcripts were of abnormal size and present in lower than normal amounts. These findings suggest that this defect in T cell receptor-CD3 expression involves a mutation in the CD3 epsilon gene leading to the synthesis of an abnormal and unstable CD3 epsilon subunit.

Antigens, CD↗
PubMed1991

Immunodeficiency with low expression of the T cell receptor/CD3 complex. Effect on T lymphocyte activation.

We report the consequences of low expression of the T cell receptor (TcR)/CD3 complex by T lymphocytes from a 4-year-old boy with a mild immunodeficiency. TcR/CD3 expression was found to be deficient on both resting and activated T cells, using both anti-CD3 and anti-TcR alpha/beta monoclonal antibodies. As shown by immunofluorescence and immunoprecipitation studies, residual expression (corresponding to about 10% of normal) was detectable on resting and activated TcR alpha/beta+ T cells. Other T cell membrane receptors were normally expressed. The functional consequences of this TcR/CD3 expression deficiency included an absence of T cell proliferation, interleukin 2 receptor expression and calcium flux following anti-CD3 and anti-CD2 antibody-triggered T cell activation. Antigen (tetanus toxoid, Candida and allogeneic cell)-induced proliferation was detectable. In contrast, cytotoxic T cell activity towards allogeneic cells was deficient. These findings shed light on the function of the TcR/CD3 complex and indicate that the expression of a limited number of TcR/CD3 receptors may be sufficient to trigger antigen-specific T cell activation (and, possibly, differentiation) and that anti-CD3 antibody-induced T cell activation differs somewhat from antigen/major histocompatibility complex molecule-induced activation. These results also confirm that the CD2 pathway of T cell activation is CD3 dependent.

Antigens, CD↗
PubMed1991

Lymphocyte subsets in whole blood and isolated mononuclear leucocytes of healthy infants and children.

The determination of lymphocyte subsets utilizing monoclonal antibodies and flow cytometry has become essential in the evaluation of immunological status. Using a standardized method it was found that in healthy children the percentage of CD 8+ (Leu 2+) positive cells increases significantly (P less than 0.01) during infancy, whereas the percentage of CD 4+ (Leu 3+) positive cells decreases with age (P less than 0.01). The percentage of CD 3+ (Leu 4+) cells remains constant. The ratio of CD 4/CD 8 positive cells is significantly (P less than 0.001) higher in infants than in older children. Other subpopulations (HLA DR+, Leu 7) were found to be constant in all age groups. For the comparison of data on lymphocyte subsets obtained by flow cytometry a standardized test procedure is important.

Adolescent↗
PubMed1991

Primary membrane T cell immunodeficiencies.

Primary membrane T cell immunodeficiencies (ID) have recently been characterized. In this paper we describe the main findings about the leukocyte adhesion deficiencies (LAD), the ID with low expression of the T cell receptor/CD3 complex, and the Omenn's syndrome. LAD is a consequence of mutations in the beta-chain-encoding gene of the leukocyte adhesion proteins. Functional consequences mainly affect phagocytic cells which are incapable of transendothelial migration. Effector T lymphocyte functions are, however, also impaired, i.e., helper T cell activity and cytotoxicity. The latter defect may account for the inability of LAD patients to reject HLA nonidentical bone marrow. Low expression of the T cell receptor CD3 complex is a rare entity characterized by a profoundly diminished expression of the whole complex on all T cells. The basic defect has not yet been unravelled. Interestingly, such T cells differentiate normally and can be activated by some antigens while anti-CD3 and anti-CD2 antibodies are not efficient. In five patients with Omenn's syndrome (combined immunodeficiency with eosinophilia), oligoclonal T cells were detected in blood, skin, and gut. These T cells are also in vivo activated. Since in one family, one sibling presented with typical SCID, i.e., alymphocytosis, and another with the Omenn's syndrome, it is proposed that the latter syndrome may correspond to a form of leakiness of SCID as found in the mice SCID model.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Renal changes in cytomegalovirus infection.

Renal biopsy was performed in 20 graft recipients to characterise the histological features associated with poor renal function concomitant with cytomegalovirus infection (CMV). Eight patients presented with proteinuria, three had microscopic haematuria at onset, and five were hypertensive. Infection was accompanied by clinical symptoms (fever, leucopenia, mild hepatic damage, or pneumonitis) in 15 patients. In all cases, serum creatinine was greater than 2 mg/dl. All patients showed some glomerular alteration on biopsy, and vascular changes were the predominant feature in seven cases. IgM and complement (C3) were found in the glomeruli of five of six patients studied by immunofluorescence. Serum creatinine was below 2 mg/dl at ten to 26 months following the infectious episode in four patients and between 2-3 mg/dl in three patients. The remaining 13 developed irreversible rejection and end-stage renal failure. We conclude that CMV, the most commonly recognised viral infection following transplantation, can cause renal changes, both glomerular (CMV glomerulopathy) and vascular (transplant vasculopathy), which may induce poor graft function.

Antibodies, Viral↗
PubMed1977

[Immunsuppression under vitamin B6 deficiency (author's transl)].

The influence of a Vitamin B6 free diet and the effect of Desoxipyridoxin (a potent Vitamin B6 Antagonist) on the immunesystem of mice was investigated in several experimental setups. Rejection times of skintransplants from inbred strains (129 J) on C57bl/6J mice served as a model for immunosuppression. Rejection times under alimentary Vitamin B6 deficiency did not exceed those under hypocaloric nutrition associated with comparable weight loss. Immunosuppression with the Vitamin B6 antagonist Desoxipyridoxin was much more pronounced. The effect was related to the duration of treatment. Desoxipyridoxin offers the possibility of effective immunsuppression, which is readily reversible.

Animals↗