Expression of the CD4+ cell-specific chemoattractant interleukin-16 in mycosis fungoides.
Interleukin-16 is a soluble ligand to the CD4 molecule with chemotactic properties for CD4+ cells and a competence growth factor for CD4+ T cells, upregulating HLA-DR and the interleukin-2 receptor CD25. There is also evidence for a synergistic effect of interleukin-16 and interleukin-2 on the activation of CD4+ T cells. The infiltrate in mycosis fungoides, the most common cutaneous T cell lymphoma, is typically CD4+. We tested the possibility that interleukin-16 is involved in the formation and progression of these lesions. By reverse transcription-polymerase chain reaction, interleukin-16 mRNA was detected in 18 of 18 mycosis fungoides lesions investigated. By competitive reverse transcription-polymerase chain reaction, interleukin-16 mRNA expression increased with disease stage. Secreted interleukin-16 was detected by enzyme-linked immunosorbent assay in both Th1- and Th2-like T cell clones (as characterized by their production of interferon-gamma and interleukin-4) grown from lesional dermis and epidermis. By immunohistochemistry and in situ hybridization, infiltrating lymphocytes were the main producers of interleukin-16 whereas keratinocytes and endothelial cells remained negative. Atypical cells with convoluted nuclei were also positive. In advanced mycosis fungoides stages, many blast-like cells were positive, but some larger blasts remained negative. Interleukin-16 expression correlated positively with the expression of interleukin-2 and its receptor CD25 in individual skin lesions. Interleukin-2 expression, however, was weak or absent in samples from uninvolved skin, healthy controls and lesional psoriasis. Given the biologic properties of interleukin-16 and the parallel activation of the interleukin-2/CD25 pathway, interleukin-16 might be involved in the recruitment and stimulation of CD4+ lymphocytes in mycosis fungoides lesions and therefore contribute to the perpetuation of the associated cutaneous inflammation.
Blaschke
V
V
Department of Dermatology, Georg-August-University, Göttingen, Germany. vblasch@gwdg.de
Reich
K
K
Middel
P
P
Letschert
M
M
Sachse
F
F
Harwix
S
S
Neumann
C
C
D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019410:Interleukin-16 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000032:analysis; D009182:Mycosis Fungoides / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000276:immunology*
D019410:Interleukin-16; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2