Antigen-Specific CD4 T Cell and B Cell Responses to Borrelia burgdorferi.
J Immunol
; 211(6): 994-1005, 2023 09 15.
Article
en En
| MEDLINE
| ID: mdl-37556156
ABSTRACT
Long-lived T-dependent B cell responses fail to develop during persistent infection of mice with Borrelia burgdorferi, the causative agent of Lyme disease, raising questions about the induction and/or functionality of anti-B. burgdorferi adaptive immune responses. Yet, a lack of reagents has limited investigations into B. burgdorferi-specific T and B cells. We attempted two approaches to track B. burgdorferi-induced CD4 T cells. First, a B. burgdorferi mutant was generated with an influenza hemagglutinin (HA) peptide, HA111-119, inserted into the B. burgdorferi arthritis-related protein (Arp) locus. Although this B. burgdorferi arpHA strain remained infectious, peptide-specific TCR transgenic CD4 T cells in vitro, or adoptively transferred into B. burgdorferi arpHA-infected BALB/c mice, did not clonally expand above those of recipients infected with the parental B. burgdorferi strain or a B. burgdorferi mutant containing an irrelevant peptide. Some expansion, however, occurred in B. burgdorferi arpHA-infected BALB/c SCID mice. Second, a (to our knowledge) newly identified I-Ab-restricted CD4 T cell epitope, Arp152-166, was used to generate Arp MHC class II tetramers. Flow cytometry showed small numbers of Arp-specific CD4 T cells emerging in mice infected with B. burgdorferi but not with Arp-deficient Borrelia afzelii. Although up to 30% of Arp-specific CD4 T cells were ICOS+PD-1+CXCR5+BCL6+ T follicular helper cells, their numbers declined after day 12, before germinal centers (GCs) are prominent. Although some Arp-specific B cells, identified using fluorochrome-labeled rArp proteins, had the phenotype of GC B cells, their frequencies did not correlate with anti-Arp serum IgG. The data suggest a failure not in the induction, but in the maintenance of GC T follicular helper and/or B cells to B. burgdorferi.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Lyme
/
Borrelia burgdorferi
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Canadá