Peptide-specific T helper cells identified by MHC class II tetramers differentiate into several subtypes upon immunization with CAF01 adjuvanted H56 tuberculosis vaccine formulation.
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.
Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biotecnologie Mediche, Università di Siena, Siena, Italy.
Gennaro
G
Prota
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Dennis
D
Christensen
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Peter
P
Andersen
Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biotecnologie Mediche, Università di Siena, Siena, Italy.
Donata
D
Medaglini
Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biotecnologie Mediche, Università di Siena, Siena, Italy. Electronic address: annalisa.ciabattini@unisi.it.
Annalisa
A
Ciabattini
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit
CD4(+) T cell priming; MHC class II tetramers; Subcutaneous immunization; T helper subsets