The Characteristics Of Peripheral Lymphocyte Subsets In Adult Onset Infectious Mononucleosis And Chronic Active Epstein-Barr Virus Infection Patients

Objective:The aim of this study is to investigate the characteristics of peripheral lymphocyte subsets in adult onset infectious mononucleosis(IM)and chronic active Epstein-Barr virus infection(CAEB V)patients,and compare the status of immune functions in two immunopathological diseases.Methods:Blood samples were collected from IM patients at the acute phase,one and six months follow-up.and CAEBV patients after confirmed diagnosis.Profile of peripheral lymphocyte subsets were analyzed with flow cytometry.Results:Ten patients were enrolled in the IM group,six of which finished one-month follow-up and two finished six-month follow-up.Six CAEBV patients and ten healthy donors were involved in the study.Compared to healthy controls(HC),a large magnitude of CD8+T cell expansion is observed(IM vs,HC 3706.32±1433.70,68.1±11.6%vs.553.30±112.00,26.3 ±5.3%,p<0.0001),along with substantial increase of memory CD4+T cells(76.0±9.6%vs.51.3±11.9%,p<0.0001).T cells are highly activated(CD38+CD8+T:88.3±8.0%vs.14.7± 10.5%,p<0.0001;HLA-DR+CD8+T,77.7 ±7.7%vs.11.0±5.9%,p<0.0001)and proliferative(Ki67+CD8+T:23.6 ±10.3%vs.1.0±2.4%p<0.0001),and the level of PD-1 expression on T cells is overly increased(PD-1+CD4+T:34.7±11.1%vs.11.6±4.4%:PD-1+CD8+T:31.2±13.6%vs.1 1.8±6.3%,p<0.0001).Symptoms were all resolved after one month in IM patients,and lymphocyte subsets and cell marker expressions returned to normal levels.In CAEBV patients,cell count of lymphocyte subsets were substantially decreased,and the percentage of memory CD4+T cells mildly elevated(CAEBV vs.HC 72.2±24.2%vs.51.3 ±11.9%,p=0.0186).CD8+T cells were slightly activated(CD38+CD8+T:45.5±23.7%vs.14.7 ±10.5%,p<0.0001;HLA-DR+CD8+T,51.6±21.6%vs.1 1.0 ±5.9%,p<0.0001),but no increased level of Ki67+expression,a proliferative marker,was observed.PD-1 expression on T cells was significantly upregulated(PD-1+CD4+T:33.6± 14.3%vs.11.6±4.4%,p=0.0101;PD-1+CD8+T:31.2±19.4%vs.1 1.8 ±6.3%,p=0.0412).In comparison of two groups,the cell count and activation levels of CD8+T cells are remarkably higher(IM vs.CAEBV,3706.3±1433.7 vs.124.3±83.5,p<0.0001 CD8+CD38+:88.3 ± 8.0%vs.45.4 ±23.7%.p<0.0001;CD8+HLA-DR+:77.7±7.7 vs.51.6±21.6,p=0.0093).Conclusion:1.IM is the results of overreactive T-cell response,when CD8+T cells are highly proliferative and dramatically expanded.T cells are highly activated and level of terminal differentiation is increased at this stage.PD-1 expression is correspondingly upregulated in this process to limit tissue damages due to hyperactivated immune response.One month after,the immune system returns to its normal state.2.In CAEBV patients,immune functions,especially T cell response,are severely impaired with substantial decrease of lymphocyte numbers.Even though a mild activation of T cells is observed,proliferation and terminal differentiation of T cells are probably inhibited due to elevated level of PD-1 expression.T cell exabit a few characteristic of early T cell exhaustion.3.In comparison of lymphocyte subsets in IM and CAEBV patients,distinct different is observed in terms of cell count and activation levels of CD8+T cells.This data shows that flow cytometry based T cell response evaluation have the potential to be valuable tools in EBV infection prognosis.