INTRODUCTIONKT cells comprise a lymphocytesubgroup, which was originally defined in

19871. Mouse and human NKT cells aresimilar; mice express a member of NKR-P1receptor family where as humans express areceptor called NKR-P1A (CD161)2,3. NKR-P1Ais a lectin molecule on human NK cells4. NKTcells also express TCRα chain and are foundin different tissue and organs in numbershowever the normal counts in humanperipheral blood is unknown2. Many studieshave shown that these cells play important rolein protecting vital organs and self tissues fromdamaging by inflammatory type immuneresponses1.

When these cells are activated, theyproduce IL-4 and IFN-γ and they affect theadaptive immune response. They have aparticular role in initiating and regulating theimmune response (5). Several studies have

demonstrated the importance of NKT cells inimmunregulation and in prevention ofautoimmune diseases in mice6,7,8.

It was shown that, NKT cells have a role inprotecting the development of inflammatoryautoimmune disease such as type I diabetes orencephalomyelitis. This can be related to IL-4production of NKT cells9.

It is not known, whether these cells whichhave a protecting role on autoimmune disease,do have an activator role on allergic disease. Inan experimental model it was shown that in theabsence of VαI4 NKT cell, allergen inducedairway (AHR) hyperreactivity did not develop.This study indicated that the development ofAHR after respiratory exposure depends onthe activation of pulmonary NKT cells thatproduce IL-4 and IL-1310.

Inhaled antigens induce NKT cells toactivate a Th2 response leading to IL-4 and IL-13 production. There is no consensus,

NKT Cell Levels in Patients with Type-I Hypersensitivity

FULYA �LHAN, AHMET GÖDEKMERDAN, HANDAN AKBULUT, VEDAT BULUT

F�rat University, Faculty of Medicine, Department of Immunology, Elaz�¤, Turkey

Natural killer T cells (NKT) express both NK receptors CD56, CD161, the latter being a member of the killer activatorreceptor (KAR) family and all express TCR α chain. These cells can rapidly produce interleukin 4 (IL-4) and interferongamma (IFN-γ). NKT cells have a regulatory role on the immune system. In this study we compared NK and NKT cellslevels between patient and control group. The patient group included those with type I hypersensitivity (19 rhinitis and17 asthma patient, total 36). Our results showed that both rhinitis and asthma patients displayed NKT cells levelshigher than controls. But with NK cells no difference were found between patient and control groups. These resultsindicate that these cells may play an important role in the development of asthma and rhinitis.

Turk J Immunol, 2005; 10: 9-12

Key Words: NKT cells, asthma, allergic rhinitis

9

N

Table 1: Mean ratio of NK and NKT cells in patientsand control groups

Healthy controls Asthma Allergic rhinitis

NK cell ratio (%) 12,64 ± 5,33 15,9 ± 1,97 10,9 ± 1,12

NKT cell ratio (%) 2,17 ± 1,37 7,71 ± 3,86 7,62 ± 4,54

however, on how NKT cells prevent or lead todisease and what the underlying mechanismsare that cause cytokine release to induceAHR(11)

.

The aim of this study is to determine NKand NKT cell levels in patients with type-1hypersensitivity (allergic rhinitis, asthma).

MATERIALS AND METHODS:Thirty six patients with type-1

hypersensitivity (allergic rhinitis 19, asthma 17)admitted to the out patient clinics of ourhospital were included in this study. Patients�blood samples were compared to bloodsamples of 36 healthy volunteers. Bloodsamples were collected in tubes containingEDTA. All samples were examined within twohours. Peripheral blood cells were stained forcell surface markers with monoclonalantibodies using standard methods. Thesecells were stained with isotopic controls (IgG1-FITC/IgG2a-PE) and for lymphocyte gatingwith CD45-FITC/CD14-PE. We obtained aCD45+ cell ratio of %95 or higher. We usedCD3-FITC (IM2076 Coulter ImmunotechFrance), CD56-PE (IM1281 Coulter,Immunotech France) monoclonal antibodies.Flow cytometrical analysis were made onCoulter EPICS XL-MCL (Beckman CoultereU.S.A). We examined the ratios of NK (cellsexpressing only CD3-CD16+56+) and NKT(which cells express CD3+CD16+56+ cells inblood of patients and controls. Statisticalanalysis of the data was performed usingSPSS version 10.0(SPSS inc).The Mann-Whitney-U test used for comparing the twogroups.

RESULTSNKT cells in asthma and allergic rhinitis

patients were significantly increased whencompared with healthy controls (p<0,001)(Figure 1 and 2). NKT cell ratios were similar inasthma and rhinitis group (p>0.05).

We observed NK cells ratios in asthmapatients were higher than rhinitis group (p<0.05). But no significant difference was foundin NK ratios between patients and controls.

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Figure 1. NKT cell ratio in type-1 hypersensitivitypatient

Figure 2. NKT cell ratio in healthy controls

DISCUSSIONThe function of NKT cells is still a subject of

speculation, although they might serve toregulate localized conditions and help to driveT cell differentiation in order to generate morerapidly matured responses11.

NKT cells have the capacity to rapidlyproduce a spectrum of cytokines, including IL-4, IL-10, IL-13, IFN-γ and TNF-α upon TCRengagement12.

NKT cells can promptly produce largeamounts of IL-4 and they have regulatory rolein initiation of the Th2 cell differentiation13, IL-4and IL-13 have a critical role on asthma andNKT cells can influence processing asthma.Akbari et al.10 showed that in the absence ofVα14i NKT cells, allergen induced airwayhyperactivity (AHR) did not develop. Theyindicated that the development of AHR afterrespiratory exposure requires the activation ofpulmonary NKT cells that produce IL-4 and IL-1310.

In order to determine whether NKT cellsplay the regulatory role in the pathogenesis ofhuman Th2 cell-mediated atopic disease weanalyzed the frequency of CD3+CD16+56+ Tcells in patients with asthma and allergicrhinitis. We examined peripheral blood NKTcell levels in type-I hypersensitivity patients.We found a highly significant differencebetween NKT cells of the patients and that ofthe healthy volunteers. In our patient groupNKT cell ratios were significantly higher thanthe control group. Our results show that alsoperipheral NKT cells may take part in type Ihypersensitivity. There are conflicting resultsin different studies about NKT ratios in asthmaand allergic dermatitis patients13. Magnan etal14 reported that the number of CD4+Vα2+4NKT cells were increased in allergic dermatitispatients. On the contrary, Oishi et al15 reportedthat in patients with atopic disease (6 asthma

and 3 atopic dermatitis) the number of doublenegative Vα2+4 NKT cells were greatlydiminished. Our data support the report ofMagnan et al14 and our results also show thatperipheral NKT cells are increased and playan important role in the development ofallergic rhinitis and asthma patients.

Asthma is caused by an inappropriatelyaggressive type of immune response, or Th2response, to inhaled irritants. Th2 cells alone,are not sufficient to induce asthma, NKT cellsmay be the potential co-effector cells in thedevelopment of asthma. We thought they havean important role in the pathogenesis ofasthma and allergic rhinitis. These NKT cellsmay be logical targets of asthma therapy in thefuture. The increased NKT cells induce Th2type immune response via the synthesis of IL-4 and also cause increased secretion of IgE.These cells which are thought to take part inthe pathogenesis of the disease might be usedas targets in developing new therapeuticoptions.

Correspondence: Fulya IlhanF�rat University Medical FacultyF�rat Research Center Immunology DepartmentElaz�¤/TURKEYE-mail: fulhan23@yahoo.comFax:+90 424 2379138

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