Expression of the CD4(+) cell-specific chemoattractant interleukin-16 in mycosis fungoides

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.