| Background The EB virus is generally susceptible in the normal population.Most children have no clinical symptoms after primary infection,especially children under 6 years old is mostly hidden or light incidence,but in puberty and adolescence,about 50%of primary infections are manifested as infectious mononucleosis(Infectious mononucleosis,IM),IM is the EB virus infection of immune cells(Mainly B lymphocytes)leading to disease caused by immune dysfunction,serious person can then infect T lymphocytes and NK cells of EB virus associated hemophagocytic syndrome(EB virus correlates with Haemophilus syndrome,EBV-HLH)and endanger life.Immune cell surface expression of a variety of immunosuppressive factors,including Programmed death 1(PD-1)and Programmed death 1 ligand(PD-L1),Cytotoxic T lymphocyte antigen 4(CTLA-4),T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains(TIGIT),and activated by binding with the corresponding ligand to inhibit the proliferation of immune cells the down-regulation of immune response,so as to achieve the immunosuppressive effect.Therefore,the infectious mononucleosis is closely related to the cellular immune suppression of the body.Objective To explore the expression level and significance of PD-1/PD-L1,CTLA-4 and TIGIT in different cells(including B,CD4~+T,CD8~+T and NK cells)in infectious mononucleosis.Methods In 59 cases of infectious mononucleosis in April 2017 to September 2017 in Hunan Children’s Hospital were increased in patients as the research object(informed consent),both in the acute phase of blood,including 34 patients in the recovery of blood;20 cases of healthy children as control group(Normal control,NC).Using flow cytometry to detect PD-1,PD-L1,CTLA-4 and TIGIT at different stages of the above disease in patients with different cells(including B,CD4~+T,CD8~+T and NK cells)on the expression level of observation in different stages of disease with and without change,and its expression and the comparison of liver function injury,as well as with EB virus DNA content,the correlation of thermal process.Results Results 1.PD-1/PD-L1:(1)The comparison of expression level of PD-1/PD-L1 in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cells)in the IM patients and control group:Compared with the control group(0.7±0.8)%,(18.8±6.5)%,(35.7±25.1)%,(3.4±2.9)%,the expression of PD-1 in the IM acute phase group was increased in B,CD4~+T,CD8~+T and NK cells,respectively(5.0±3.7)%,(40.3±11.5)%,(73.4±13.3)%,(9.3±12.8)%(all P<0.05),the expression of PD-1 in the IM recovery group X was increased on CD4~+T and CD8~+T cells,respectively(36.7±13.6)%,(59.9±22.0)%(all P<0.05),the expression of PD-1 in B and NK cells was no significant difference(all P>0.05).Compared with IM recovery group(1.7±2.0)%,(36.7±13.6)%,(59.9±22.0)%,(6.2±6.0)%,the expression of PD-1 in the IM acute phase group was increased in B,CD8~+T cells,respectively(5.0±3.7)%,(73.4±13.3)%(all P<0.05),the expression of PD-1in CD4~+T and NK cells was no significant difference(all P>0.05).Compared with the control group(0.9±0.9)%,(0.4±0.7)%,(1.1±2.6)%,(1.1±1.1)%,the expression of PD-L1 in the IM acute phase group was increased in B cell(7.8±6.0)%(P<0.05),the expression of PD-L1 in CD4~+T、CD8~+T and NK cells was no significant difference(all P>0.05),the expression of PD-L1 in the IM recovery group was increased in B and NK cells,respectively(4.8±6.3)%,(6.4±13.7)%(all P<0.05).Compared w i t h I M r e c o v e r y g r o u p(4.8±6.3)%,(2.0±8.3)%,(5.2±11.2)%,(6.4±13.7)%,the expression of PD-L1 in the IM acute phase group was no significant difference on B,CD4~+T,CD8~+T and NK cells(all P>0.05).(2)The comparison of the expression level of PD-1/PD-L1 in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cells)in the hepatitis and non-hepatitis group of IM patients:Compared with non-hepatitis g r o u p(4.3±2.5)%,(3 7.7±11.6)%,(6 9.5±9.7)%,(5.7±3.6)%,t h e expression level of PD-1 in hepatitis group was no significant difference on B,CD4~+T,CD8~+T and NK cells(t=0.976,P=0.333;t=1.303,P=0.198;t=1.732,P=0.089;t=1.587,P=0.118);Compared with non-hepatitis group(7.5±6.2)%,(0.6±0.9)%,(3.2±4.1)%,(2.6±2.2)%,the expression level of PD-L1 in hepatitis group was no significant difference on B,CD4~+T,CD8~+T and NK cells(t=0.212,P=0.833;t=0.551,P=0.584;t=0.781,P=0.438;t=0.111,P=0.912).(3)The interrelationship between that expression level of PD-1/PD-L1 in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cell)of IM patients and EBV-DNA quantification:The interrelationship between that expression level of PD-1 in B,CD4~+T,CD8~+T and NK cells of IM patients and EBV-DNA quantification was not significanted(r=0.049,P=0.723;r=-0.223,P=0.105;r=-0.223,P=0.119;r=-0.100,P=0.471);the interrelationship between chat expression level of PD-L1 in B,CD4~+T,CD8~+T and NK cells and EBV-DNA quantification was not significanted(r=0.068,P=0.625;r=-0.021,P=0.881;r=0.026,P=0.851;r=-0.068,P=0.623);(4)The interrelationship between that expression level of PD-1/PD-L1 in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cell)of IM patients and thermal process:the interrelationship between that expression level of PD-1 in B,CD4~+T,CD8~+T and NK cells of IM patients and thermal process was not significanted(r=0.166,P=0.209;r=-0.0 7 1,P=0.5 9 4;r=0.0 4 8.P=0.7 1 8;r=0.0 3 1,P=0.8 1 6);t h e interrelationship between that expression level of PD-L1 in B,CD4~+T,CD8~+T and NK cells of IM patients and thermal process was not significanted(r=-0.065,P=0.624;r=-0.102,P=0.444;r=0.065,P=0.624;XII r=0.133,P=0.316).3.CTLA-4:(1)The comparison of expression level of CTLA-4 in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cells)in the IM p a t i e n t s a n d c o n t r o l g r o u p:C o m p a r e d w i t h t h e c o n t r o l group(0.5±0.5)%,(1.4±1.7)%,(1.2±1.8)%,(1.6±1.6)%,the expression of CTLA-4 in the IM acute phase group was increased in B,CD4~+T cells,respectively(3.7±7.1)%,(6.9±10.3)%(all P<0.05),the expression of CTLA-4 in CD8~+T,NK cells was no significant difference(all P>0.05),the expression of CTLA-4 in the IM recovery group was no significant difference on B,CD4~+T,CD8~+T and NK cells(all P>0.05);Compared with IM recovery group(1.8±2.7)%,(5.2±6.2)%,(5.9±17.8)%,(7.3±12.4)%,the expression of CTLA-4 in the IM acute phase group was no significant difference on B,CD4~+T,CD8~+T and NK cells(all P>0.05);(2)The comparison of the expression level of CTLA-4 in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cells)in the hepatitis and non-hepatitis group of IM patients:Compared with non-hepatitis group(2.8±4.7)%,(5.6±9.7)%,(4.9±12.5)%,(5.6±8.3)%,the expression level of CTLA-4 in hepatitis group was no significant difference on B,CD4~+T,CD8~+T and NK cells(t=0.678,P=0.500;t=0.736,P=0.465;t=0.617,P=0.540;t=0.852,P=0.398).(3)The interrelationship between that e x p r e s s i o n l e v e l o f C T L A-4 i n d i f f e r e n t p e r i p h e r a l b l o o d cells(B,CD4~+T,CD8~+T and NK cell)of IM patients and EBV-DNA quantification:The interrelationship between that expression level of CTLA-4 in B,CD4~+T,CD8~+T and NK cells of IM patients and EBV-DNA quantification was not significanted(r=0.662,P=0.659;r=-0.048,P=0.731;r=-0.036,P=0.798;r=-0.037,P=0.792).(4)Theinterrelationship between that expression level of CTLA-4 in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cell)of IM patients and thermal process:the interrelationship between that expression level of CTLA-4 in B,CD4~+T,CD8~+T and NK cells of IM patients and thermal process was not significanted(r=-0.103,P=0.437;r=-0.148,P=0.265;r=0.047,P=0.726;r=-0.078,P=0.556).4.TIGIT:(1)The comparison of expression level of TIGIT in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cells)in the IM patients and control group:Compared with the con trol group(2.3±1.3%,(13.6±7.0)%,(18.4±8.9)%,(57.4±10.8)%,the expression of TIGIT in the IM acute phase group was increased in B,CD4~+T,CD8~+T and NK cells,respectively(9.8±6.9)%,(25.2±10.7)%,(43.7±14.6)%,(68.7±10.4)%(all P<0.05),the expression of TIGIT in the IM recovery group was increased in B,CD4~+T and CD8~+T cells,Respectively(6.3±6.8)%,(28.4±19.3)%,(39.5±18.5)%(all P<0.05),the expression level of TIGIT in NK cells was no significant difference(P>0.05);Compared with IM recovery group(6.3±6.8)%,(28.4±19.3)%,(39.5±18.5)%,(63.3±14.8)%,the expression level of TIGIT in the IM acute phase group XIV was no significant difference on B,CD4~+T,CD8~+T and NK cells(all P>0.05).(2)The comparison of the expression level of TIGIT in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cells)in the hepatitis and non-hepatitis group of IM patients:Compared with non-hepatitis(11.7±7.9)%,(23.7±11.5)%,(42.7±13.6)%,(67.4±11.2)%,th-e expression level of TIGIT in hepatitis group was no significant difference on B,CD4~+T,CD8~+T and NK cells(t=-1.577,P=0.120;t=0.789,P=0.433;t=0.412,P=0.682;t=0.708,P=0.482).(3)The interrelationship between that e x p r e s s i o n l e v e l o f T I G I T i n d i f f e r e n t p e r i p h e r a l b l o o d cells(B,CD4~+T,CD8~+T and NK cell)of IM patients and EBV-DNA quantification:The expression level of TIGIT in B cells was positively correlated with EBV-DNA quantification(r=0.371,P=0.006),the interrelationship between that expression level of TIGIT in CD4~+T,CD8~+T and NK cells of IM patients and EBV-DNA quantification was not significanted(r=-0.040,P=0.775;r=0.044,P=0.754;r=-0.127,P=0.362).(4)The interrelationship between that expression level of TIGIT in different peripheral blood cells(B,CD4~+T,CD8~+T and NK cell)of IM patients and thermal process:the interrelationship between that expression level of TIGIT in B,CD4~+T,CD8~+T and NK cells of IM patients and thermal process was not significanted((r=-0.010,P=0.938;r=0.002,P=0.988;r=0.017,P=0.900;r=-0.147,P=0.267).Conclusion (1)The expression of PD-1,PD-L1,CTLA-4 and TIGIT in the infectious mononucleosis was up-regulated in the acute phase of the disease,and the expression decreased with the recovery of the disease.This study suggests that it may be involved in the pathogenesis of infectious mononucleosis;(2)The expression level of TIGIT was positively correlated with EBV-DNA quantification;(3)PD-1,PD-L1,CTLA-4 and TIGIT may not participate in the mechanism of liver function injury;and Their level of expression was not correlated with the thermal process. |
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