Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma
Pablo Vieyra-Garcia, Jack D. Crouch, John T. O’Malley, Edward W. Seger, Chao H. Yang, Jessica E. Teague, Anna Maria Vromans, Ahmed Gehad, Thet Su Win, Zizi Yu, Elizabeth L. Lowry, Jung-Im Na, Alain H. Rook, Peter Wolf, Rachael A. Clark
Pablo Vieyra-Garcia, Jack D. Crouch, John T. O’Malley, Edward W. Seger, Chao H. Yang, Jessica E. Teague, Anna Maria Vromans, Ahmed Gehad, Thet Su Win, Zizi Yu, Elizabeth L. Lowry, Jung-Im Na, Alain H. Rook, Peter Wolf, Rachael A. Clark
View: Text | PDF
Research Article Dermatology Immunology

Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma

  • Text
  • PDF
Abstract

Psoralen plus UVA (PUVA) is an effective therapy for mycosis fungoides (MF), the skin-limited variant of cutaneous T cell lymphoma (CTCL). In low-burden patients, PUVA reduced or eradicated malignant T cells and induced clonal expansion of CD8+ T cells associated with malignant T cell depletion. High-burden patients appeared to clinically improve but large numbers of malignant T cells persisted in skin. Clinical improvement was linked to turnover of benign T cell clones but not to malignant T cell reduction. Benign T cells were associated with the Th2-recruiting chemokine CCL18 before therapy and with the Th1-recruiting chemokines CXCL9, CXCL10, and CXCL11 after therapy, suggesting a switch from Th2 to Th1. Inflammation was correlated with OX40L and CD40L gene expression; immunostaining localized these receptors to CCL18-expressing c-Kit+ dendritic cells that clustered together with CD40+OX40+ benign and CD40+CD40L+ malignant T cells, creating a proinflammatory synapse in skin. Our data suggest that visible inflammation in CTCL results from the recruitment and activation of benign T cells by c-Kit+OX40L+CD40L+ dendritic cells and that this activation may provide tumorigenic signals. Targeting c-Kit, OX40, and CD40 signaling may be novel therapeutic avenues for the treatment of MF.

Authors

Pablo Vieyra-Garcia, Jack D. Crouch, John T. O’Malley, Edward W. Seger, Chao H. Yang, Jessica E. Teague, Anna Maria Vromans, Ahmed Gehad, Thet Su Win, Zizi Yu, Elizabeth L. Lowry, Jung-Im Na, Alain H. Rook, Peter Wolf, Rachael A. Clark

×

Figure 2

Visible inflammation does not reflect malignant T cell burden and reduced inflammation is linked to turnover of benign T cells.

Options: View larger image (or click on image) Download as PowerPoint
Visible inflammation does not reflect malignant T cell burden and reduce...
(A) Clinical exam scores in high- and low-burden patients were not significantly different. (B) Two patients are shown in whom visible inflammation (clinical exam scores) improved but the malignant T cell clone remained high after treatment (patient 1, 68%; patient 4, 69%) or even increased (patient 4). (C) Malignant T cell frequency remained high after treatment despite the presence of large numbers of malignant T cells in skin in patient 4, a complete clinical responder. The unique TCR CDR3 sequences of each nonmalignant T cell clone were used to identify which benign T cells persisted after therapy (blue), were eliminated from skin (light green), or were recruited to skin (dark green) after therapy. Persistent benign clones were benign T cell clones that were present in skin both before and after PUVA therapy. (D) Additional patients are shown in whom the malignant T cell burden remained high after therapy despite improvement in clinical inflammation exam scores. (E–H) Improvement in inflammation is correlated with a shift in the benign T cell population but not with depletion of malignant T cells. Improvement in inflammation (mSWAT) did not correlate with reductions in the number of malignant T cells (E), total T cells (F), or benign T cells (G). However, the loss of specific T cell clones from skin and recruitment of a second, distinct T cell population was correlated with reduced inflammation as assessed by mSWAT (H) and CAILS scores (Supplemental Figure 1). Differences between 2 sample groups were detected using the 1-tailed Wilcoxon-Mann-Whitney test (α = 0.05). For correlations, a Pearson’s correlation coefficient with a 2-tailed P value is reported.

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts