Abstract
BackgroundHuman parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously.Methods and FindingsThe number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA–peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%–0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low.ConclusionThis is the first example to our knowledge of an “acute” human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation—analogous to that for cytomegalovirus infection—is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.
Highlights
Human parvovirus human parvovirus B19 (B19) (B19) is a ubiquitous, single-stranded DNA virus
Individuals tested many years after infection exhibited lower frequencies of B19specific cytotoxic T lymphocytes, typically 0.05%–0.5% of CD8þ T cells, which were perforin, CD38, and CCR7 low. This is the first example to our knowledge of an ‘‘acute’’ human viral infection inducing a persistent activated CD8þ T cell response
CD8þ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development
Summary
Human parvovirus B19 (B19) is a ubiquitous, single-stranded DNA virus. The 5.6-kb genome codes for only three major proteins, the two overlapping capsid proteins VP1 and VP2 and the non-structural protein NS1. Amongst the viral infections studied, cytomegalovirus (CMV) is associated with the emergence of the largest long-term memory populations with the most ‘‘mature’’ phenotype, CD27/CD28 low, CD57 high, and often perforin positive [9]. The factors that determine the phenotype and function of these populations of lymphocytes are not fully understood, but continued exposure to antigen is thought to be important Persistent infections such as hepatitis C virus (HCV), Epstein– Barr virus (EBV), and HIV show antiviral populations that are ‘‘effector’’ (CD62L or CCR7 low), but show lower levels of maturation than CMV-specific responses [7]. Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The authors wanted to study one part of the immune system—T cells—in people who had just recently been infected with the virus and compare the findings with people who had had the infection a long time previously
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