Aberrant cytokine production by Sezary syndrome patients: cytokine secretion pattern resembles murine Th2 cells.
Sezary syndrome (SzS), the leukemic stage of cutaneous T-cell lymphoma (CTCL), is typically a CD4+ T-cell lympho-proliferative disease characterized by numerous immunologic abnormalities, including decreased T-cell responses to antigens and mitogens, decreased natural killer and lymphocyte-activated killer cell activities, eosinophilia, and increased levels of immunoglobulins, particularly IgE and IgA. Because this constellation of abnormalities is reminiscent of the pleiotropic in vitro activities of IL-4 and IL-5, we examined the possibility that malignant T cells in SzS may be producing increased amounts of IL-4 with a concomitant decrease in IL-2 and IFN-gamma production. Such a cytokine secretion pattern would be similar to that produced by murine Th2 cells. Serum IL-4 enzyme-linked immunosorbent assay measurements revealed that 33% of SzS patients (n = 21) had levels of IL-4 significantly higher (mean, 7.2 pg/ml; range, 0-48, p less than 0.05) than normal controls (mean, 1.59; range, 0-3.1). Although the majority of tested patients had elevated serum IgE, no direct correlation between serum IL-4 levels and serum IgE levels was observed. Peripheral blood mononuclear cells (PBMC) isolated from SzS patients and stimulated with phytohemagglutinin (PHA) produced significantly higher levels of interleukin (IL)-4 and significantly lower levels of IL-2 and interferon (IFN)-gamma than did PBMC from normal controls (p less than 0.02, p less than 0.05, and p less than 0.02, respectively). PBMC from SzS patients in remission produced IL-4 and IL-2 levels similar to that of the normal controls. To determine if IFN-gamma could inhibit the increased IL-4 production by PHA-stimulated PBMC from SzS patients, IFN-gamma was added to culture at 0, 24, or 48 h prior to the addition of PHA. Significant decreases in IL-4 production were seen only in cultures incubated with IFN-gamma for 24 and 48 h prior to the addition of PHA. IL-2 levels were not affected by IFN-gamma incubation. The increased IL-4 and decreased IL-2 and IFN-gamma production by PBMC from SzS patients suggests that Sezary cells have a cytokine profile similar to murine Th2 cells. Moreover, this cytokine secretion pattern may play an integral role in the immunopathogenesis of advanced CTCL. The results also suggest that IFN-gamma be a useful component in the spectrum of therapeutic approaches to SzS.
Vowels
B R
BR
Department of Dermatology, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Cassin
M
M
Vonderheid
E C
EC
Rook
A H
AH
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D012751:Sezary Syndrome / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D013601:T-Lymphocytes / Q000473:pathology
D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma