Cytotoxic T-lymphocyte antigen 4 blockade augments the T-cell response primed by attenuated Listeria monocytogenes resulting in more rapid clearance of virulent bacterial challenge.
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) uniformly suppresses antigen-specific T cells during chronic infection with bacterial, parasitic or viral pathogens. However, the importance of CTLA-4 in controlling the T-cell response during acute infection or after priming with live attenuated vaccine vectors has not been well characterized. Since strategies aimed at blocking CTLA-4 are being actively developed to therapeutically augment T-cell-mediated immunity, the effects of CTLA-4 blockade on T-cell activation during these conditions need to be more clearly defined. We have examined the role of CTLA-4 in a prime-challenge model of acute bacterial infection using both attenuated and virulent strains of the intracellular bacterium Listeria monocytogenes. Although Foxp3(+) CD4(+) T cells are the predominant CTLA-4-expressing cell type in naïve mice, antigen-specific Foxp3(-) CD4(+) cells upregulate CTLA-4 expression after primary L. monocytogenes infection. Blockade of CTLA-4 results in increased numbers of L. monocytogenes-specific CD4 and CD8 T cells after primary infection with attenuated L. monocytogenes, and confers more rapid bacterial clearance after secondary challenge with virulent L. monocytogenes. Accordingly, CTLA-4 plays an important suppressive role in T-cell priming and protective immunity in a prime-challenge model of acute bacterial infection.
Rowe
Jared H
JH
Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Johanns
Tanner M
TM
Ertelt
James M
JM
Lai
Joseph C
JC
Way
Sing Sing
SS
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D060908:CTLA-4 Antigen; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000382:microbiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001427:Bacterial Toxins; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C110366:OVA-8; D010446:Peptide Fragments; D010455:Peptides; D010047:Ovalbumin; C038705:hlyA protein, Listeria monocytogenes