Tumor necrosis factor-alpha and interferon-gamma, but not HTLV-I tax, are likely factors in the epidermotropism of cutaneous T-cell lymphoma via induction of interferon-inducible protein-10.
We have previously shown that Interferon-Inducible Protein-10 (IP-10), a cytokine chemotactic for CD4-positive lymphocytes, is overexpressed by lesional epidermal keratinocytes and probably accounts for the epidermotropism of cutaneous T-cell lymphoma (CTCL). The tax gene of human T-lymphotropic virus-I (HTLV-I) immortalizes CD4-positive lymphocytes, induces IFN-gamma, and has been detected in patients with classical CTCL who are seronegative for HTLV-I. TNF-alpha is synergistic with IFN-gamma for the induction of IP-10. We therefore decided to define the presence of tax, IFN-gamma, TNF-alpha, and IP-10 in lesions of 19 adults with classical CTCL who were seronegative for HTLV-I. Lesional mRNAs for actin, TNF-alpha, IFN-gamma, and tax were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) amplification. In addition IP-10, TNF-alpha, and IFN-gamma were detected and localized with immunocytochemistry of frozen sections. In agreement with previous observations IP-10 was overexpressed in lesional keratinocytes of all 19 patients. By RT-PCR, mRNA for IFN-gamma was detected in lesions of 8, and for TNF-alpha in lesions of 13 patients. By immunocytochemistry, TNF-alpha was expressed by lesional keratinocytes in 10 of 13 tested patients, whereas IFN-gamma was focally expressed by lesional lymphocytes and faintly by lesional keratinocytes in 9 of 13 tested patients. tax mRNA was not detected in lesions of any patient, but was easily detectable in cutaneous lesions or peripheral blood of control patients who were seropositive for HTLV-I. We conclude that TNF-alpha and IFN-gamma may cause epidermotropism by inducing IP-10. However, the tax gene of HTLV-I does not appear to be involved in the pathogenesis of classical CTCL.
Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
D
D
Daliani
R A
RA
Ulmer
C
C
Jackow
W
W
Pugh
B
B
Gansbacher
F
F
Cabanillas
M
M
Duvic
A H
AH
Sarris
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000032:analysis*; D005260:Female; D016356:Gene Products, tax / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D016410:Lymphoma, T-Cell, Cutaneous / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D018523:Tropism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016356:Gene Products, tax; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma