Tumor-infiltrating lymphocytes (TILs) were isolated from a patient with disseminated melanoma during active specific immunotherapy. Purified CD8+ TILs lysed autologous melanoma cells and one of three allogeneic melanoma cell lines. CD4+ TILs also lysed melanoma cell lines, but cytotoxicity was considerably lower than with CD8+ cultures. Neither the CD4+ nor the CD8+ culture lysed autologous EBV-transformed B cells in a 6- or 14-hr assay. These data were confirmed using CD4+ or CD8+ TIL clones. Coculture of autologous melanoma cells with rIFN-γ (100 U/ml) for 24 hr significantly enhanced cytolysis by CD4+ clones from 1.5-fold to more than 10-fold. This enhancement was associated in part with an increased cell surface expression of HLA class II molecules, because lysis by seven of nine CD4+ clones was almost completely blocked by anti-HLA class II MAb L227. Interestingly, both anti-HLA class I and anti-HLA class II MAbs blocked cytolysis by four of the nine CD4+ clones. Lysis by two CD4+ clones was blocked by anti-HLA class I MAb w6/32, but not by L227. The CD4 molecule was involved in the binding to HLA class II molecules or in signal transduction, since anti-CD4 MAb consistently inhibited cytotoxicity. Blocking of the known accessory molecule-ligand interactions CD11a,CD18 (LFA-1)-CD54 (ICAM-1 or -2) and CD2-CD58 (LFA-3) demonstrated the involvement of both interactions in the cytotoxicity by CD4+ clones. CD4+ CTLs may be important effector cells in vivo against melanomas expressing HLA class I and/or class II molecules.
|Number of pages||13|
|State||Published - Dec 1 1993|