Peptide-specific T Helper Cells Identified by MHC Class II Tetramers Differentiate Into Several Subtypes Upon Immunization With CAF01 Adjuvanted H56 Tuberculosis Vaccine Formulation

Vaccine. 2015 Nov 27;33(48):6823-30. doi: 10.1016/j.vaccine.2015.09.024. Epub 2015 Oct 20.

Abstract

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.

Keywords: CD4(+) T cell priming; MHC class II tetramers; Subcutaneous immunization; T helper subsets.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Female
  • Histocompatibility Antigens Class II / metabolism*
  • Lung / immunology
  • Lymph Nodes / immunology
  • Mice, Inbred C57BL
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Tuberculosis Vaccines / administration & dosage*
  • Tuberculosis Vaccines / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Histocompatibility Antigens Class II
  • Tuberculosis Vaccines
  • Vaccines, Subunit