Mycosis fungoides exhibits a Th1-type cell-mediated cytokine profile whereas Sezary syndrome expresses a Th2-type profile.
We determined T-cell cytokine profiles in the epidermis, dermis, and blood of cutaneous T-cell lymphoma to differentiate whether unique cytokine profiles were associated with mycosis fungoides (MF) versus Sezary syndrome. Punch biopsy specimens from plaque stage MF (n = 7) were compared to Sezary skin (n = 3) after undergoing rapid heat-saline separation of epidermis from dermis. Normal adult skin (n = 11), neonatal foreskin (n = 4), untreated psoriatic plaques (n = 6), and normal donor peripheral blood leukocytes (n = 3) were studied as controls. Total RNA was extracted from all skin specimens, as well as peripheral blood leukocytes from MF (n = 3) and Sezary patients (n = 7), and was converted to cDNA by reverse transcriptase. Polymerase chain reaction amplification of cDNAs using interleukin 2 (IL-2), IL-4, IL-5, IL-10, and interferon gamma-specific primers was used to differentiate Th1-type responses (IL-2+ and interferon gamma +) from Th2-type responses (IL-4+, IL-5+, and IL-10+). beta-actin specific primers were included as a positive control for mRNA integrity. All MF specimens contained mRNAs for IL-2 and interferon gamma limited to epidermis but not IL-4, IL-5, or IL-10. In contrast, Sezary skin and blood showed a cytokine mRNA pattern dominated by IL-4, IL-5, and IL-10. MF blood showed a pattern similar to normal peripheral blood T cells with mixed detection of all T-helper cell cytokine mRNAs. All psoriasis samples contained mRNAs for IL-2 and interferon gamma in both epidermis and dermis with no IL-4 or IL-10 in either compartment. These findings demonstrate that the cutaneous lesions of MF are characterized by an epidermal Th1-type cytokine profile, whereas both the blood and skin of patients with Sezary syndrome is characterized by a Th2-type profile. This work suggests that differences in cytokine production may be related to the pathophysiology and clinical presentation in cutaneous T-cell lymphoma.
Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202.
G
G
Saed
D P
DP
Fivenson
Y
Y
Naidu
B J
BJ
Nickoloff
D001483:Base Sequence; D001706:Biopsy; D015139:Blotting, Southern; D016207:Cytokines / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009182:Mycosis Fungoides / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012751:Sezary Syndrome / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; D004273:DNA, Neoplasm; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma