Age and HIV perturb the TB Immunity in Regulatory and Cytotoxic Subpopulations of NKT cells

Abstract

Abstract In the pre-antibiotic era, ~20% of Tuberculosis (TB) patients overcame the disease without therapy, implying host immunity can sometimes control disease. The risk of disease progression is higher among HIV-infected individuals and children, therefore we evaluate how HIV and age alter the balance of cytotoxic versus immune regulatory NKT immune phenotype in individuals with TB and latent Mycobacterium tuberculosis infection (LTBi). We evaluated the NKT immune response from 49 individuals with TB (25 HIV-infected) and 48 with asymptomatic LTBi (14 HIV-infected). Using flow cytometry based multi-dimensional immune profiling, we analyzed the expression level of previously described determinants of NKT cytotoxicity (CD3dim) and immune regulatory (CD3bright) phenotype and function. CD3bright NKT cell population was correlated with age during children TB (p = 0.002). This cell type had increased in adults with TB (p = 0.034), but not in children. Also, high level of perforin producing CD3bright NKT cells had increased in adults with TB compare to adults with LTBi (p = 0.004). On the other hand, CD3dim NKT cell had no age correlation nor difference between TB and LTBi participants. While HIV-infected LTBi individuals had decreased perforin production in CD3dim NKT cells (p = 0.012). CD3bright and CD3dim NKT sub-populations previously reported influence regulatory versus cytotoxic function. We demonstrate that age and HIV status of participants have effected to regulatory and cytotoxic function, respectively. This suggested that these two factors have different mechanisms, decreasing perforin high producing CD3bright NKT cells and decreasing perforin production in CD3dim NKT, which promote TB disease progression.