Phenotype of the anti-Rickettsia CD8+ T cell response suggests cellular correlates of protection for the assessment of novel antigens

Erika Caro-Gomez, Michal Gazi, Maria A. Cespedes, Yenny Goez, Bruno Teixeira, Gustavo Valbuena

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The obligately intracellular bacteria Rickettsia infect endothelial cells and cause systemic febrile diseases that are potentially lethal. No vaccines are currently available and current knowledge of the effective immune response is limited. Natural and experimental rickettsial infections provide strong and cross-protective cellular immunity if the infected individual survives the acute infection. Although resistance to rickettsial infections is attributed to the induction of antigen-specific T cells, particularly CD8+ T cells, the identification and validation of correlates of protective cellular immunity against rickettsial infections, an important step toward vaccine validation, remains a gap in this field. Here, we show that after a primary challenge with Rickettsia typhi in the C3H mouse model, the peak of anti-Rickettsia CD8+ T cell-mediated responses occurs 7 days post-infection (dpi), which coincides with the beginning of rickettsial clearance. At this time point, both effector-type and memory-type CD8+ T cells are present, suggesting that 7 dpi is a valid time point for the assessment of CD8+ T cell responses of mice previously immunized with protective antigens. Based on our results, we suggest four correlates of cellular protection for the assessment of protective rickettsial antigens: (1) production of IFN-γ by antigen-experienced CD3+CD8+CD44high cells, (2) production of Granzyme B by CD27lowCD43low antigen-experienced CD8+ T cells, (3) generation of memory-type CD8+ T cells [Memory Precursor Effector Cells (MPECs), as well as CD127highCD43low, and CD27highCD43low CD8+ T cells], and (4) generation of effector-like memory CD8+ T cells (CD27lowCD43low). We propose that these correlates could be useful for the general assessment of the quality of the CD8+ T cell immune response induced by novel antigens with potential use in a vaccine against Rickettsia.

Original languageEnglish (US)
Pages (from-to)4960-4967
Number of pages8
JournalVaccine
Volume32
Issue number39
DOIs
StatePublished - Sep 3 2014

Fingerprint

Rickettsia
T-lymphocytes
antigens
T-Lymphocytes
Phenotype
Antigens
phenotype
rickettsial diseases
Infection
Vaccines
Cellular Immunity
vaccines
cell-mediated immunity
Rickettsia typhi
T-Lymphoid Precursor Cells
CD3 Antigens
CD8 Antigens
immune response
cross immunity
Granzymes

Keywords

  • Antigens
  • Memory
  • Rickettsia
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine
  • Medicine(all)

Cite this

Phenotype of the anti-Rickettsia CD8+ T cell response suggests cellular correlates of protection for the assessment of novel antigens. / Caro-Gomez, Erika; Gazi, Michal; Cespedes, Maria A.; Goez, Yenny; Teixeira, Bruno; Valbuena, Gustavo.

In: Vaccine, Vol. 32, No. 39, 03.09.2014, p. 4960-4967.

Research output: Contribution to journalArticle

Caro-Gomez, Erika ; Gazi, Michal ; Cespedes, Maria A. ; Goez, Yenny ; Teixeira, Bruno ; Valbuena, Gustavo. / Phenotype of the anti-Rickettsia CD8+ T cell response suggests cellular correlates of protection for the assessment of novel antigens. In: Vaccine. 2014 ; Vol. 32, No. 39. pp. 4960-4967.
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AU - Teixeira, Bruno

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AB - The obligately intracellular bacteria Rickettsia infect endothelial cells and cause systemic febrile diseases that are potentially lethal. No vaccines are currently available and current knowledge of the effective immune response is limited. Natural and experimental rickettsial infections provide strong and cross-protective cellular immunity if the infected individual survives the acute infection. Although resistance to rickettsial infections is attributed to the induction of antigen-specific T cells, particularly CD8+ T cells, the identification and validation of correlates of protective cellular immunity against rickettsial infections, an important step toward vaccine validation, remains a gap in this field. Here, we show that after a primary challenge with Rickettsia typhi in the C3H mouse model, the peak of anti-Rickettsia CD8+ T cell-mediated responses occurs 7 days post-infection (dpi), which coincides with the beginning of rickettsial clearance. At this time point, both effector-type and memory-type CD8+ T cells are present, suggesting that 7 dpi is a valid time point for the assessment of CD8+ T cell responses of mice previously immunized with protective antigens. Based on our results, we suggest four correlates of cellular protection for the assessment of protective rickettsial antigens: (1) production of IFN-γ by antigen-experienced CD3+CD8+CD44high cells, (2) production of Granzyme B by CD27lowCD43low antigen-experienced CD8+ T cells, (3) generation of memory-type CD8+ T cells [Memory Precursor Effector Cells (MPECs), as well as CD127highCD43low, and CD27highCD43low CD8+ T cells], and (4) generation of effector-like memory CD8+ T cells (CD27lowCD43low). We propose that these correlates could be useful for the general assessment of the quality of the CD8+ T cell immune response induced by novel antigens with potential use in a vaccine against Rickettsia.

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