Dysregulated synthesis of intracellular type 1 and type 2 cytokines by T cells of patients with cutaneous T-cell lymphoma.
Mycosis fungoides (MF) and Sezary syndrome (SS) are the two main clinical entities of cutaneous T-cell lymphoma (CTCL). As the disease progresses from MF to SS, a switch from a type 1 (interleukin [IL]-2 and gamma interferon [IFN-gamma]) to a type 2 (IL-4) cytokine production profile occurs. Although roles for type 1 and type 2 cytokines in the pathogenesis of CTCL have been proposed, the cellular origins of these cytokines are unclear. Using flow cytometry to identify individual T-cell subsets, we studied cytokine synthesis by the T cells of 13 patients with SS and 12 with MF and 9 hematologically healthy donors. Upon activation with phorbol 12-myristate 13-acetate (PMA), the numbers of T cells synthesizing IL-2 were similar for all study groups. Whereas the predominant T-cell producing IL-2 in healthy donors and in those with MF was CD7(+), in patients with SS, it was CD7(-). Although the number of IL-4(+) CD4(+) T cells was low for all study groups, there was a significantly higher number of IL-4(+) CD8(+) T cells in patients with MF than in those with SS or healthy donors. There was a decline in the number of IFN-gamma-producing T cells in CTCL donors compared to that in healthy donors. More importantly, there was a significant decrease in the number of IFN-gamma-producing T cells with disease progression from MF to SS. The inability of these T cells to synthesize IFN-gamma may have prognostic value in CTCL, since it may be responsible for the progression of the disease from MF to SS.
Lee
B N
BN
Division of Pathology and Laboratory Medicine, Division of Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Duvic
M
M
Tang
C K
CK
Bueso-Ramos
C
C
Estrov
Z
Z
Reuben
J M
JM
D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis* / Q000145:classification; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology*; D009182:Mycosis Fungoides / Q000276:immunology; D011379:Prognosis; D012751:Sezary Syndrome / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate