PHENOTYPIC AND FUNCTIONAL-CHARACTERIZATION OF HUMAN-LYMPHOCYTES ACTIVATED BY INTERLEUKIN-2 TO DIRECTLY INHIBIT GROWTH OF CRYPTOCOCCUS-NEOFORMANS INVITRO

Recently we demonstrated that the nonadherent (to plastic) fraction of human PBMC could be activated by IL-2 to inhibit Cryptococcus neoform ans growth. Here we characterize the antifungal effector cells. Deplet ion by panning of natural killer (NK) (CD16+, CD56+) cells from nylon wool-treated, IL-2-activated PBMC markedly decreased lytic activity ag ainst a tumor cell target (K562) but did not affect antifungal activit y. Panning out T (CD3+, CD5+) cells enhanced activity against tumor ce lls but partially abrogated activity against C. neoformans. IL-2-activ ated T cells of 95% purity, obtained by panning out NK cells from PBMC forming rosettes with sheep erythrocytes, had excellent antifungal ac tivity but suboptimal antitumor activity. The nonrosetted cells (which were virtually free of T cells and enriched for NK cells) had both an titumor and antifungal activity, even if cultured without IL-2. CD4+, CD8+, and CD56+ cells, purified by positive selection by panning, dire ctly inhibited cryptococcal growth. Conjugate formation between fungi and both CD56+ and CD5+ effector cells was demonstrated by videomicros copy and immunoperoxidase staining. Thus, IL-2-activated T cells and N K cells form conjugates with and directly inhibit the growth of C. neo formans. To our knowledge, these data are the first demonstration of h uman T cells directly inhibiting growth of a microbial target.