文摘
CD4+ T-cell priming is an essential step in vaccination due to the key role of T helper cells in driving both effector and memory immune responses. Here we have characterized in C57BL/6 mice the T helper subtype differentiation among tetramer-specific CD4+ T cells primed by subcutaneous immunization with the tuberculosis vaccine antigen H56 plus the adjuvant CAF01. Peptide-specific population identified by the MHC class II tetramers differentiated into several T helper subtypes upon antigen encounter, and the frequency of subpopulations differed according to their localization. Th1 (CXCR3+T-bet+), Tfh (CXCR5+PD-1+Bcl-6+) and RORγt+ cells were induced in the lymph nodes draining the immunization site (dLN), while Th1 cells were the predominant subtype in the spleen. In addition, CD4+ T cells co-expressing multiple T-cell lineage-specifying transcription factors were also detected. In the lungs, most of the tetramer-binding T cells were RORγt+, while Tfh and Th1 cells were absent. After boosting, a higher frequency of tetramer-binding cells co-expressing the markers CD44 and CD127 was detected compared to primed cells, and cells showed a prevalent Th1 phenotype in both dLN and spleens, while Tfh cells were significantly reduced. In conclusion, these data demonstrate that parenteral immunization with H56 and CAF01 elicits a distribution of antigen-specific CD4+ T cells in both lymphoid tissues and lungs, and gives rise to multiple T helper subtypes, that differ depending on localization and following reactivation.
