A CD8α- Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment.
case_series · Level IV
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- Record sourced from PubMed, PMID 29499100.
- Also identified by DOI 10.1002/art.40469 and PMC identifier 6019645.
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Abstract
An unconventional population of CD4+ signaling lymphocytic activation molecule family member 7-positive (SLAMF7+) cytotoxic effector memory T (T<sub>EM</sub> ) cells (CD4+ cytotoxic T lymphocytes [CTLs]) has been linked causally to IgG4-related disease (IgG4-RD). Glucocorticoids represent the first-line therapeutic approach in patients with IgG4-RD, but their mechanism of action in this specific condition remains unknown. We undertook this study to determine the impact of glucocorticoids on CD4+ CTLs in IgG4-RD. Expression of CD8α, granzyme A, perforin, and SLAMF7 within the effector memory compartment of CD45RO+ (T<sub>EM</sub> ) and CD45RA+ effector memory T (T<sub>EMRA</sub> ) CD4+ cells was quantified by flow cytometry in 18 patients with active IgG4-RD, both at baseline and after 6 months of glucocorticoid treatment. Eighteen healthy subjects were studied as controls. Next-generation sequencing of the T cell receptor α- and β-chain gene was performed on circulating CD4+ CTLs from patients with IgG4-RD before and after treatment and in affected tissues. Circulating CD4+ T<sub>EM</sub> and T<sub>EMRA</sub> cells were not expanded in IgG4-RD patients compared to healthy controls. CD4+SLAMF7+ T<sub>EM</sub> cells (but not T<sub>EMRA</sub> cells) were significantly increased among IgG4-RD patients. Within CD4+SLAMF7+ T<sub>EM</sub> cells, CD8α- cells but not CD8α<sup>low</sup> cells were elevated in IgG4-RD patients. The same dominant clones of CD8α-CD4+SLAMF7+ T<sub>EM</sub> cells found in peripheral blood were also identified in affected tissue. CD8α- and CD8α<sup>low</sup> CD4+SLAMF7+ T<sub>EM</sub> cells both expressed cytolytic molecules. Clonally expanded CD8α- but not CD8α<sup>low</sup> CD4+SLAMF7+ T<sub>EM</sub> cells decreased following glucocorticoid-induced disease remission. A subset of CD8α-CD4+SLAMF7+ cytotoxic T<sub>EM</sub> cells is oligoclonally expanded in patients with active IgG4-RD. This T<sub>EM</sub> cell population contracts following glucocorticoid-induced remission. Further characterization of this cell population may provide prognostic information and targets for therapeutic intervention.
Medical subject headings
- CD4-Positive T-Lymphocytes
- CD8 Antigens
- Glucocorticoids
- Immunoglobulin G4-Related Disease
- Signaling Lymphocytic Activation Molecule Family
- T-Lymphocytes, Cytotoxic