Differential CD4+and CD8+T cell recognition of mycobacteria antigens in pediatric versus adult TB

T cells from young children may be limited in capacity to mount pro-inflammatory responses to intracellular pathogens, thus contributing to vulnerability to TB disease. We compared CD4+ and CD8+ T cell cytokine production in response to mycobacterial antigens and mitogen SEB, between Ugandan children <5 yr (PedTB) and adults (ATB) with culture-confirmed pulmonary TB. HIV-uninfected children (n=12) and adults (n=41) had blood drawn for PBMC isolation prior to TB treatment. CD4+ and CD8+ T cell production of IFNγ, IL2, and TNFα in response to ESAT6/CFP10 (EC), ESXJ, PE12/13, PE3, PPE15, and PPE51 peptide pools, and SEB, were assessed by intracellular flow cytometry. Proportions and frequencies of CD4+ and CD8+ T cells producing cytokines were compared using Fisher’s Exact and Kruskal-Wallis tests, respectively, with adjusted p-values <0.05 significant. PedTB and ATB had equivalent CD4+ and CD8+ T cell production of IFNγ, IL2, and TNFα, including polyfunctional responses, to EC. T cell cytokine responses to ESXJ and PPE51 were equivalent; significant differences were noted in CD4+ T cell responses to PE3 and PPE15, and CD8+ T cell responses to PE12/13. Frequencies of CD4+ T cells producing IFNγ or IL2 in response to SEB were lower (p<0.0001) in PedTB versus ATB. Young children with PedTB exhibited adult-like capacity to generate Th-1 cytokines in response to EC, ESXJ, and PPE 51. Pediatric responses to PE3, PPE15, and PE12/13 were impaired, suggesting that the breath of antigen recognition differs between infants and adults with TB. Differential T cell recognition of mycobacterial antigens between adults and children should be considered in development of novel T cell based diagnostics and vaccines targeting pediatric TB. Supporting from grants by NIH: AI157807; HHSN272200900053C