Regulation of B and T cell development by anterior pituitary hormones

Hormones produced by the anterior pituitary gland have been implicated in the regulation of primary lymphocyte development. In order to identify endocrine factors involved in that process, several strains of mice with genetic defects resulting in a selective impairment in the production of one or more anterior pituitary-derived hormones have been analysed. This study has resulted in the classification of endocrine hormones into the following four categories (i) hormones such as prolactin with no apparent effects on primary lymphopoiesis; (ii) anabolic hormones such as growth hormone and insulin-like growth factor-I whose stimulatory effects on primary lymphopoiesis are non-lineage-specific and related to their actions as systemic mediators of growth and/or differentiation; (iii) hormones such as thyroid hormones that have an obligate role in primary B lymphopoiesis; and (iv) hormones such as oestrogens that act as negative regulators of lymphopoiesis.     

T cell and T cell subset determination in normal peripheral blood: Comparison of the indirect immunofluorescence and lymphocytotoxicity techniques

Summary We compared a simple complement-dependent lymphocytotoxicity test with a widely used indirect immunofluorescence procedure to enumerate total T, T helper, and T suppressor lymphocytes in normal blood samples. Results with the two techniques were closely similar.     

T cell and T cell subset determination in normal peripheral blood: comparison of the indirect immunofluorescence and lymphocytotoxicity techniques

We compared a simple complement-dependent lymphocytotoxicity test with a widely used indirect immunofluorescence procedure to enumerate total T, T helper, and T suppressor lymphocytes in normal blood samples. Results with the two techniques were closely similar.     

Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire

Human cytomegalovirus (HCMV) infection or reactivation is a cause of morbidity and mortality in immunocompromised individuals. In immunocompetent individuals, in contrast, HCMV is successfully controlled by specific CD8 and CD4 T cells. Knowledge of CD8 and CD4 T cell epitopes from HCMV and their immunodominant features is crucial for the generation of epitope-specific T cells for adoptive immunotherapy and for the development of a peptide-based HCMV vaccine. Therefore, we investigated the natural frequencies of a large number of CD8 and CD4 T cell epitopes, including 10 novel ones. We determined several epitopes as immunodominant. Surprisingly, no clear hierarchies were found for CD8 T cell epitopes, indicating codominance. These results will be valuable for adoptive transfer strategies and support initiatives towards development of a peptide-based HCMV vaccine.Received 12 August 2004; received after revision 24 September 2004; accepted 29 October 2004 These authors contributed equally to this work.     

Glucocorticoids in T cell apoptosis and function

Glucocorticoids (GCs) are a class of steroid hormones which regulate a variety of essential biological functions. The profound anti-inflammatory and immunosuppressive activity of synthetic GCs, combined with their power to induce lymphocyte apoptosis place them among the most commonly prescribed drugs worldwide. Endogenous GCs also exert a wide range of immunomodulatory activities, including the control of T cell homeostasis. Most, if not all of these effects are mediated through the glucocorticoid receptor, a member of the nuclear receptor superfamily. However, the signaling pathways and their cell type specificity remain poorly defined. In this review, we summarize our present knowledge on GC action, the mechanisms employed to induce apoptosis and the currently discussed models of how they may participate in thymocyte development. Although our knowledge in this field has substantially increased during recent years, we are still far from a comprehensive picture of the role that GCs play in T lymphocytes. Received 20 August 2005; received after revision 27 September 2005; accepted 10 October 2005     

The persistence of T cell memory

T cell memory is a crucial feature of the adaptive immune system in the defense against pathogens. During the last years, numerous studies have focused their efforts on uncovering the signals, inflammatory cues, and extracellular factors that support memory differentiation. This research is beginning to decipher the complex gene network that controls memory programming. However, how the different signals, that a T cell receives during the process of differentiation, interplay to trigger memory programming is still poorly defined. In this review, we focus on the most recent advances in the field and discuss how T cell receptor signaling and inflammation control CD8 memory differentiation.     

Effect of the mast cell disruptor B.W. 48/80 on dietary atherosclerosis in the male rabbit

Zusammenfassung Mit Cholesterin ernährte Kaninchen, denen gleichzeitig Compound 48/80 injiziert wurde, wiesen gegenüber nur mit Cholesterinzusatz gefütterten Tieren geringere Atheromatose des Aortenbogens auf. Compound 48/80 rief auch eine Verminderung des Serumcholesteringehaltes hervor. Unter dem Einfluss von Compound 48/80 schien ein beschleunigter Abbau der atheromatösen Plaques einzusetzen bevor noch eine Verminderung des Serumcholesterins auftrat. Es wird vermutet, dass der Schutz von Compound 48/80 gegen die durch Diät erzeugte Atheromatose des Kaninchens auf einer Veränderung des arteriellen Glykosaminglykans beruht.     

The role of adapter proteins in T cell activation

Engagement of antigen receptors on lymphocytes leads to a myriad of complex signal transduction cascades. Recently, work from several laboratories has led to the identification and characterization of novel adapter molecules, proteins with no intrinsic enzymatic activity but which integrate signal transduction pathways by mediating protein-protein interactions. Interestingly, it appears that many of these adapter proteins play as critical a role as the effector enzymes themselves in both lymphocyte development and activation. This review describes some of the biochemical and molecular features of several of these newly identified hematopoietic cell-specific adapter molecules highlighting their importance in regulating (both positively and negatively) signal transduction mediated by the T cell antigen receptor.     

Impact of T cell selection methods in the success of clinical adoptive immunotherapy

Chemotherapy and/or radiotherapy regular regimens used for conditioning of recipients of hematopoietic stem cell transplantation (SCT) induce a period of transient profound immunosuppression. The onset of a competent immunological response, such as the appearance of viral-specific T cells, is associated with a lower incidence of viral infections after haematopoietic transplantation. The rapid development of immunodominant peptide virus screening together with advances in the design of genetic and non-genetic viral- and tumoural-specific cellular selection strategies have opened new strategies for cellular immunotherapy in oncologic recipients who are highly sensitive to viral infections. However, the rapid development of cellular immunotherapy in SCT has disclosed the role of the T cell selection method in the modulation of functional cell activity and of in vivo secondary effects triggered following immunotherapy.     

Heterogeneity of gangliosides among T cell subsets

Gangliosides are major components of highly organized membrane microdomains or rafts, yet little is known about the role of gangliosides in raft organization. This is also the case of gangliosides in TCR-mediated activation. Comprehensive structural analysis of gangliosides in the primary thymocytes and CD4⁺ T and CD8⁺ T cells was not achieved due to technical difficulties. We have found that CD8⁺ T cells express very high levels of o-series gangliosides, but on the other hand, CD4⁺ T cells preferably express a-series gangliosides. In the TCR-dependent activation, CD4⁺ T cells selectively require a-series gangliosides, but CD8⁺ T cells do require only o-series gangliosides but not a-series gangliosides. Ganglioside GM3 synthase-deficient mice lacking a-series gangliosides neither exhibited the TCR-dependent activation of CD4⁺ T nor developed ovalbumin-induced allergic airway inflammation. These findings imply that the distinct expression pattern of ganglioside species in CD4⁺ and CD8⁺ T cells define the immune function of each T cell subset.     

Studies on the relationships between biotin and the behaviour of B and T lymphocytes in the guinea-pig

Summary In biotin-deficient guinea-pigs the number of circulating neutrophils is increased; lymphocytes carrying B and T markers are decreased. Incubation with biotin increases significantly the number of lymphocytes carrying B and T markers, from biotin-deficient guinea-pigs; no increase was observed when the lymphocytes from normal guinea-pigs were incubated.     

Biological role of major transplantation antigens in T cell self-recognition

The proposal is made, illustrated and supported by experimental evidence that T cell-mediated immunopathology triggered initially by low- or non-cytopathic infectious agents may cause diseases, susceptibility to which is linked to the major histocompatibility gene complex.     

Biological role of major transplantation antigens in T cell self-recognition

Summary The proposal is made, illustrated and supported by experimental evidence that T cell-mediated immunopathology triggered initially by low- or non-cytopathic infectious agents may cause diseases, susceptibility to which is linked to the major histocompatibility gene complex.This summary is an updated version of the paper given on the occasion of the Paul Ehrlich Prize ceremonies in 1983; it was also presented at the meeting New Trends in Allergy II in München 1985, and is reproduced here with the permission of Springer Verlag, Heidelberg.     

Changes in the T4/T3 molar ratio following thyrotrophin releasing hormone injection in cattle

Summary The injection of thyrotropin releasing hormone into cattle resulted in a rapid decrease in the T₄/T₃ molar ratio. 2 breeds of cattle, Shorthorn and Africander Cross were studied. The decrease in the T₄/T₃ molar ratio was significantly greater in the Shorthorn breed. It is concluded that acute stimulation of the thyroid gland with TRH results in enhanced release of both T₃ and T₄ and that T₃ is discharged more rapidly than T₄.     

Dissection of cytotoxic and helper T cell responses

Cytotoxic (CD8⁺) and helper (CD4⁺) T cells play a crucial role in resolving infections by intracellular pathogens. The development of technologies to visualize antigen-specific T cell responses in mice and men over the past decade has allowed a dissection of the formation of adaptive T cell immunity. This review gives a brief overview of the currently used detection techniques and possible future additions. Furthermore, we discuss our current understanding of the formation of antigen-specific T cell responses, with particular attention to the similarities and differences in CD4⁺ and CD8⁺ T cell responses, the functional heterogeneity within responder T cell pools and the regulation of CD8⁺ T cell responses by dendritic cells and CD4⁺ helper T cells. Received 16 June 2005; received after revision 2 August 2005; accepted 15 August 2005     

The unique features of follicular T cell subsets

The germinal center (GC) reaction is critical for humoral immunity, but also contributes adversely to a variety of autoimmune diseases. While the major protective function of GCs is mediated by plasma cells and memory B cells, follicular helper T (TFH) cells represent a specialized T cell subset that provides essential help to the antigen-specific B cells in the form of membrane-bound ligands and secreted factors such as IL-21. Recent studies have revealed that TFH cells are capable of considerable functional diversity as well as possessing the ability to form memory cells. The molecular basis of this plasticity and heterogeneity is only now emerging. It has also become apparent that several other populations of follicular T cells exist, including natural killer T cells and regulatory T cells. In this review we will discuss the function of follicular T cells and interaction of these populations within the GC response.