Interleukin-16 is a soluble ligand to the CD4 molecule with chemotactic pro
perties for CD4(+) cells and a competence growth factor for CD4(+) T cells,
upregulating HLA-DR and the interleukin-2 receptor CD25, There is also evi
dence for a synergistic effect of interleukin-16 and interleukin-2 on the a
ctivation of CD4(+) T cells. The infiltrate in mycosis fungoides, the most
common cutaneous T cell lymphoma, is typically CD4(+). We tested the possib
ility that interleukin-16 is involved in the formation and progression of t
hese lesions. By reverse transcription-polymerase chain reaction, interleuk
in-16 mRNA was detected in 18 of 18 mycosis fungoides lesions investigated.
By competitive reverse transcription-polymerase chain reaction, interleuki
n-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 an
d interleukin-4) grown from lesional dermis and epidermis, By immunohistoch
emistry and in situ hybridization, infiltrating lymphocytes were the main p
roducers of interleukin-16 whereas keratinocytes and endothelial cells rema
ined negative, Atypical cells with convoluted nuclei were also positive. In
advanced mycosis fungoides stages, many blast-like cells were positive, bu
t some larger blasts remained negative. Interleukin-16 expression correlate
d positively with the expression of interleukin-2 and its receptor CD25 in
individual skin lesions. Interleukin-2 expression, however, was weak or abs
ent in samples from uninvolved skin, healthy controls and lesional psoriasi
s, Given the biologic properties of interleukin-16 and the parallel activat
ion 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 cuta
neous inflammation.