CADM1/TSLC1 Identifies HTLV-1-Infected Cells and Determines Their Susceptibility to CTL-Mediated Lysis

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Human T cell lymphotropic virus-1 (HTLV-1) infects CD4+ T cells, leading to inflammatory diseases or cancer in a subset of carriers.
• Cytotoxic T lymphocyte (CTL) responses are crucial for controlling HTLV-1 viral load and disease progression.
• Most HTLV-1-infected cells are Tax-negative, and their immunophenotype remains poorly understood, hindering analysis of CTL responses.

Purpose of the Study:

• To identify a cell-surface molecule expressed on both Tax+ and Tax-HTLV-1-infected cells.
• To utilize this marker for analyzing CTL responses in fresh peripheral blood mononuclear cells.
• To investigate the role of CADM1 in HTLV-1 infection and CTL evasion.

Main Methods:

• Screening for cell-surface markers to identify HTLV-1-infected cells.
• Utilizing flow cytometry and immunophenotyping to analyze cell populations.
• Quantifying CTL-mediated killing of infected cells (Tax+ and Tax-) expressing CADM1.
• Assessing the correlation between CADM1 expression, CTL lysis, and viral load.

Main Results:

• Cell adhesion molecule 1 (CADM1) was identified as a sensitive and specific marker for HTLV-1 infection, outperforming CD25, CCR4, and ICAM-1.
• CADM1+CD4+ T cells harbored a significant portion (median 65%) of proviral copies.
• CADM1 expression correlated with increased susceptibility of infected cells to CTL lysis, yet Tax+CADM1- cells were poorly lysed.
• Tax-CADM1+ cells showed low lysis rates with autologous CTLs but were efficiently killed with exogenous peptide antigen loading.
• Upregulation of CRTAM on CD8+ T cells correlated with efficient lysis of infected cells.

Conclusions:

• CADM1 is a robust marker for identifying HTLV-1-infected cells, including those lacking Tax expression.
• CADM1 expression influences the interaction between infected cells and CTLs, potentially aiding viral persistence.
• The findings suggest CADM1 may confer a survival advantage to HTLV-1-infected cells despite CTL pressure.