François Hentges

CD56bright natural killer (NK) cells: an important NK cell subset

Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56bright CD16dim/− and CD56dim CD16+, respectively. In this review, we will focus on the CD56bright NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56dim NK cells. CD56bright NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear.

Control of NK cell functions by CD4+CD25+ regulatory T cells

Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance. As a result of suppressive effects on CD4+ and CD8+ effector T cells, Treg control the adaptive immune system and prevent autoimmunity. In addition, they inhibit B lymphocytes, dendritic cells, and monocytes/macrophages. It is interesting that several recent papers show that CD4+CD25+ Treg are also able to inhibit NK cells. Thus, Treg exert their control on immune responses from the onset (triggering of innate immune cells) to the effector phase of adaptive immunity (B and T cell‐mediated responses). That Treg inhibit NK cells suggests that their uncontrolled activation might break self‐tolerance and induce “innate” autoimmune pathology. Conversely, Treg‐mediated suppression of NK cell functions might have negative effects, as these cells are important in defense against infections and cancer. It is conceivable that Treg might dampen efficient activation of NK cells in these diseases.

Allergic cross-reactions between cat and pig serum albumin: Study at the protein and DNA levels

After observing a patient allergic to cat dander and pork but devoid of other allergies, we prospectively screened patients known to be allergic to cat for a second sensitization to pork. After collecting the sera of 10 young patients found to contain specific IgE to cat dander and pork, we undertook this study to detect the possible cross‐reactive allergen, define its molecular characteristics, and evaluate its clinical relevance. Through immunoblotting techniques, cat and porcine serum albumin were found to be jointly recognized molecules. These findings were further analyzed by specific anti‐albumin IgE titrations and cross‐inhibition experiments. Cat serum albumin cDNA was obtained from cat liver, and the corresponding amino acid sequence was deduced and compared to the known porcine and human serum albumin sequences. Inhibition experiments showed that the spectrum of IgE reactivity to cat serum albumin completely contained IgE reactivity to porcine serum albumin, suggesting that sensitization to cat was the primary event. In two cohorts of cat‐allergic persons, the frequency of sensitization to cat serum albumin was found to lie between 14% and 23%. Sensitization to porcine albumin was found to lie between 3% and 10%. About 1/3 of these persons are likely to experience allergic symptoms in relation to pork consumption. Sensitization to cat serum albumin should be considered a useful marker of possible cross‐sensitization not only to porcine serum albumin but also to other mammalian serum albumins.

5‐HT2a receptor polymorphism gene in bipolar disorder and harm avoidance personality trait

The purpose [corrected] of this study was to investigate the relationship between bipolar disorder and the harm avoidance personality trait (HA), and the genetic contribution of the polymorphic DNA variation T102C in exon 1 of 5-HTR2a (chromosome 13q14-21) in bipolar disorder and HA personality trait. Forty bipolar patients and 89 normal subjects completed the TPQ questionnaire and were genotyped for 5-HT2a. Bipolar patients scored higher than normal subjects on the HA dimension. However, no contribution of the 5-HTR2a polymorphism on the bipolar disorder or on the HA personality trait emerged. Despite the limited sample size, these results exclude a major effect of the 5-HTR2a polymorphism on bipolar disorder and HA personality trait but not a minor effect.

Identification of enolases and aldolases as important fish allergens in cod, salmon and tuna: component resolved diagnosis using parvalbumin and the new allergens.

The majority of fish‐allergic patients are sensitized to parvalbumin, known to be the cause of important IgE cross‐reactivity among fish species. Little is known about the importance of fish allergens other than parvalbumin.

Natural killer cells in atopic and autoimmune diseases of the skin

Natural killer (NK) cells are best known for their ability to recognize and kill tumor cells and virally infected cells and for their ability to produce large amounts of some cytokines, such as IFN-gamma. Recent research has substantially expanded our view on the function of NK cells in the immune system in health and disease. In addition to the better-studied functions in cancer and autoimmunity, contributions from NK cells to allergies and various skin diseases have emerged. We briefly recount the traditional NK cell functions before focusing on their roles in atopic dermatitis, psoriasis, alopecia areata, and pemphigus vulgaris. Although this field is still developing, strong data are available that indicate NK cell involvement. In patients with allergic diseases, the production of T(H)2 cytokines by NK cells contributes to the known immune deviation. In patients with psoriasis, their pathophysiologic role seems to be especially the production of IFN-gamma. NK cell overactivation can be found in patients with alopecia areata and pemphigus vulgaris. Many details are still unclear; however, we believe that there is solid evidence that NK cells actively participate in a number of diseases that have not been traditionally linked to this type of lymphocyte.

IgE antibodies of fish allergic patients cross‐react with frog parvalbumin

Background:  The major allergens in fish are parvalbumins. Important immunoglobulin (Ig)E cross‐recognition of parvalbumins from different fish species has been shown. Recently frog parvalbumin α has been found to be responsible for a case of IgE‐mediated anaphylaxis triggered by the ingestion of frog meat. The aim of this study was to investigate whether IgE antibodies of fish allergic persons cross‐react with frog parvalbumin and to appreciate its clinical relevance.

Association between novelty‐seeking and the dopamine D3 receptor gene in bipolar patients: A preliminary report

Recent studies in healthy controls suggest an association between novelty-seeking (NS) and the dopamine D4 receptor (DRD4) gene. In this study, we further investigated the relationship between genes implicated in dopamine as well as serotonin neurotransmission and personality traits in bipolar (BP) disorder. Scores on the Tridimensional Personality Questionnaire were examined in 37 recovered Research Diagnostic Criteria-diagnosed BP patients genotyped for DRD3, DRD4, and serotonin 2A receptor (5HTR2a) polymorphisms. Carriers of DRD3 allele 1 showed significantly lower NS values compared to patients without this allele. Scores on NS and on harm-avoidance were not related to DRD4 or 5HTR2a polymorphisms. These preliminary results suggest a role for D3 receptor in NS expression in BP patients.

Important variations in parvalbumin content in common fish species: a factor possibly contributing to variable allergenicity.

Background: Although 95% of fish-allergic patients are sensitized to the major fish allergen parvalbumin, clinical reactions to different fish species vary considerably in symptoms, intensity and frequency in allergic subjects. This study aimed at the quantification of parvalbumin levels in salmon, trout, cod, carp, mackerel, herring, redfish and tuna. Methods: Fish muscle extracts were separated by SDS-PAGE and parvalbumin content was estimated by densitometric band quantification. Individual antisera were raised in BALB/c mice against parvalbumins purified from seven fish species. Parvalbumin content was quantified in fish (raw/processed) and skin prick test (SPT) solutions by ELISA using the corresponding anti-serum for detection and the purified parvalbumins as standards. Results: Using SDS-PAGE scanning, parvalbumin contents were <0.5 mg per gram tissue for mackerel, 0.5–2 mg for salmon and trout, and >2 mg for cod, carp, redfish and herring. Using ELISA, parvalbumin content ranged from <0.05 mg for tuna, 0.3–0.7 mg for mackerel, 1–2.5 mg for salmon, trout and cod to >2.5 mg per gram raw muscle for carp, herring and redfish. The parvalbumin content of processed samples (cooked/commercial) was 20–60% lower. Allergen content in SPT samples ranged from 20 to 70 µg parvalbumin/ml of extract. No parvalbumin was found in tuna SPT solution. Conclusion: The parvalbumin content of most commonly consumed fish species varies considerably. Differences range from severalfold to one hundredfold. This has to be taken into account when designing food challenge tests and advising fish-allergic patients.

Consequences of the crosstalk between monocytes/macrophages and natural killer cells

The interaction between natural killer (NK) cells and different other immune cells like T cells and dendritic cells is well-described, but the crosstalk with monocytes or macrophages and the nature of ligands/receptors implicated are just emerging. The macrophage-NK interaction is a major first-line defense against pathogens (bacteria, viruses, fungi, and parasites). The recruitment and the activation of NK cells to perform cytotoxicity or produce cytokines at the sites of inflammation are important to fight infections. The two main mechanisms by which macrophages can prime NK cells are (1) activation through soluble mediators such as IL-12, IL-18, and (2) stimulation through direct cell-to-cell contact. We will discuss the progress in matters of modulation of NK cell functions by monocytes and macrophages, in the steady state and during diseases.