The CD4+CD26- T-cell population in classical Hodgkin's lymphoma displays a distinctive regulatory T-cell profile.
Little is known about the gene expression profile and significance of the rosetting CD4+CD26- T cells in classical Hodgkin's lymphoma (cHL). To characterize these T cells, CD4+CD26- and CD4+CD26+ T-cell populations were sorted from lymph node (LN) cell suspensions from nodular sclerosis HL (NSHL) and reactive LNs. mRNA profiles of stimulated and resting cell subsets were evaluated with quantitative RT-PCR for 46 genes. We observed a higher percentage of CD4+CD26- T cells in NSHL than in reactive LNs. The resting CD4+CD26- T cells in NSHL showed higher mRNA levels of CD25, CTLA4, OX40 and CCR4 compared with in LNs, supporting a regulatory T-cell (Treg) type, and this was validated by immunohistochemistry. Moreover, these cells showed low or no expression of the Th1- or Th2-related cytokines IL-2, IFN-gamma, IL-13, IL-12B, IL-4, and IL-5, and the chemoattractant receptor CRTH2. Besides Tregs, Th17 cells may exist in NSHL based on the significantly higher IL-17 mRNA level for both T-cell populations in NSHL. Upon stimulation in vitro, lack of upregulation of mRNA levels of most cytokine genes indicated an anergic character for the CD4+CD26- T-cell subset. Anergy fits with the Treg profile of these cells, probably explaining the immunosuppressive mechanism involved in NSHL.
Ma
Yue
Y
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Visser
Lydia
L
Blokzijl
Tjasso
T
Harms
Geert
G
Atayar
Cigdem
C
Poppema
Sibrand
S
van den Berg
Anke
A
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015759:Ionomycin / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012598:Sclerosis; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012333:RNA, Messenger; D015759:Ionomycin; D018819:Dipeptidyl Peptidase 4; D013755:Tetradecanoylphorbol Acetate