Phenotypic and functional characterization of human lymphocytes activated by interleukin-2 to directly inhibit growth of Cryptococcus neoformans in vitro.
Recently we demonstrated that the nonadherent (to plastic) fraction of human PBMC could be activated by IL-2 to inhibit Cryptococcus neoformans growth. Here we characterize the antifungal effector cells. Depletion by panning of natural killer (NK) (CD16+, CD56+) cells from nylon wool-treated, IL-2-activated PBMC markedly decreased lytic activity against a tumor cell target (K562) but did not affect antifungal activity. Panning out T (CD3+, CD5+) cells enhanced activity against tumor cells but partially abrogated activity against C. neoformans. IL-2-activated T cells of 95% purity, obtained by panning out NK cells from PBMC forming rosettes with sheep erythrocytes, had excellent antifungal activity but suboptimal antitumor activity. The nonrosetted cells (which were virtually free of T cells and enriched for NK cells) had both antitumor and antifungal activity, even if cultured without IL-2. CD4+, CD8+, and CD56+ cells, purified by positive selection by panning, directly inhibited cryptococcal growth. Conjugate formation between fungi and both CD56+ and CD5+ effector cells was demonstrated by videomicroscopy and immunoperoxidase staining. Thus, IL-2-activated T cells and NK cells form conjugates with and directly inhibit the growth of C. neoformans. To our knowledge, these data are the first demonstration of human T cells directly inhibiting growth of a microbial target.
Levitz
S M
SM
Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, Massachusetts 02118.
Dupont
M P
MP
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D019002:CD56 Antigen; D016827:CD8 Antigens / Q000032:analysis; D002448:Cell Adhesion; D002469:Cell Separation / Q000379:methods; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development*; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008853:Microscopy / Q000379:methods; D009000:Monocytes / Q000166:cytology; D012397:Rosette Formation; D012756:Sheep / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D014741:Video Recording
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D016827:CD8 Antigens; D007376:Interleukin-2