High frequencies of functionally competent circulating Tax-specific CD8+ T cells in human T lymphotropic virus type 2 infection
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Published on: April 26, 2024
André L A Oliveira1, Hitoshi Hayakawa, Doris Schor
1Centre for Research in Infectious Diseases, University College Dublin, Dublin, Ireland.
Insights
Cytotoxic T lymphocyte (CTL) responses targeting the Human T lymphotropic virus type 2 (HTLV-2) Tax protein are detectable and correlate with viral load. These findings suggest CTLs play a role in controlling HTLV-2 infection.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Human T lymphotropic virus type 2 (HTLV-2) establishes persistent, often asymptomatic infections.
- Understanding the host immune response is crucial for managing HTLV-2.
- Cytotoxic T lymphocyte (CTL) responses are key components of viral control.
Purpose of the Study:
- To characterize ex vivo CTL responses against the HTLV-2 Tax protein.
- To investigate the correlation between CTL frequency, viral load, and T cell phenotype.
- To assess the functional capacity of HTLV-2 specific CTLs.
Main Methods:
- Screening of HLA-A*0201-restricted Tax2 epitopes for CTL recognition.
- Quantification of virus-specific CTL frequencies in peripheral blood.
- Analysis of T cell phenotype and cytotoxicity assays.
- Correlation analysis with proviral load.
Main Results:
- A specific CTL response was detected against the HLA-A*0201-restricted Tax2 epitope (residues 11-19).
- Virus-specific CTLs were found in most subjects, reaching up to 24% of CD8(+) T cells.
- CTL frequency positively correlated with HTLV-2 proviral load.
- Detected CTLs displayed an effector memory phenotype and potent cytotoxic activity.
Conclusions:
- A strong CTL response against HTLV-2 Tax protein is feasible and detectable ex vivo.
- CTLs may play a significant role in controlling HTLV-2 viral burden.
- Effective CTL responses could be a key factor in maintaining persistent infection and preventing disease progression.
Abstract:
Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11-19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8(+) T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8(+) T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2((11-19)) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.
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