Recombinant lemA without adjuvant induces extensive expansion of H2-M3-restricted CD8 effectors, which can suppress primary listeriosis in mice

• Published in: International immunology Vol. 14; no. 2; pp. 225 - 232
• Main Authors: Tawab, Abdul, Fields, Janet, Chao, Elizabeth, Kurlander, Roger J.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2002; Oxford Publishing Limited (England)
• Subjects: Amino Acid Sequence; Animals; Bacterial Proteins - chemistry; Bacterial Proteins - pharmacology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; g-Interferon; histocompatibility antigen H-2; Histocompatibility Antigens Class I - immunology; host resistance; Immunization, Passive; Immunologic Memory; l-glutamine; LemA protein; Listeria monocytogenes; Listeriosis - prevention & control; LM Listeria monocytogenes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Molecular Sequence Data; OVA ovalbumin; passive immunization; penicillin; peptide-specific CD8 T cells; primary immune response; R10 RPMI 1640 supplemented with FCS; Recombinant Proteins - pharmacology; Species Specificity; streptomycin and 2-mercaptoethanol
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/14.2.225

Mice infected with Listeria monocytogenes (LM) produce large numbers of H2-M3-restricted CD8 T cells directed against the formylated peptides, f-MIGWII and f-MIVIL. To examine responsiveness to these epitopes in the absence of infection, we inoculated mice with recombinant lemA (r-lemA) containing f-MIGWII or r-vemA (a variant of r-lemA containing f-MIVIL in place of f-MIGWII) without adjuvant. To monitor responses, we measured peptide-specific cytoplasmic IFN-γ production ex vivo by freshly harvested splenocytes at varying times post-inoculation. B6 mice inoculated with r-lemA produced substantial numbers of epitope-specific CD8 cells with peak levels on day 7 when there were 1.1 × 106 f-MIGWII-specific CD8 cells in the spleen (8.2% of total CD8 splenocytes). The r-vemA-treated animals accumulated 0.25 × 106 cells (1.8% of total CD8 cells) at this time point. Comparable responses were observed after rechallenge of immunized animals. Other elements in the lemA moiety distinct from the immunogenic peptide were required since mice did not respond to equimolar amounts of synthetic f-MIGWII or f-MIVIL alone. In comparative studies, B6 and C3H/HeJ mice responded to r-lemA much more vigorously than BALB/c animals. When r-lemA- or r-vemA-treated B6 animals were challenged i.v. with LM 7 days later, they suppressed splenic accumulation of bacteria much more effectively than controls. On the other hand, antigen-treated animals were not protected against infection 1 month later. Thus, responsive strains of mice respond vigorously to H2-M3-restricted epitopes, even in the absence of bacterial infection or adjuvant. The resulting effectors acutely enhance antimicrobial resistance but do not confer long-term memory protection.