Phenotypic and functional characterization of human lymphocytes activated by interleukin-2 to directly inhibit growth of Cryptococcus neoformans in vitro

• Published in: The Journal of clinical investigation Vol. 91; no. 4; pp. 1490 - 1498
• Main Authors: LEVITZ, S. M, DUPONT, M. P
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.04.1993
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antigens, CD - analysis; Antigens, Differentiation, T-Lymphocyte - analysis; Biological and medical sciences; CD56 Antigen; CD8 Antigens - analysis; Cell Adhesion; Cell Separation - methods; Cryptococcus neoformans; Cryptococcus neoformans - drug effects; Cryptococcus neoformans - growth & development; Erythrocytes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunoenzyme Techniques; Interleukin-2 - pharmacology; Killer Cells, Natural - immunology; Leukocytes, Mononuclear - cytology; Lymphocyte Activation - drug effects; Lymphokines, interleukins ( function, expression); Microscopy - methods; Monocytes - cytology; Regulatory factors and their cellular receptors; Rosette Formation; Sheep - blood; T-Lymphocytes - immunology; Fungi; Infection; Natural killer cell; Human; Cryptococcus neoformans; Interleukin 2; Mycosis; T-Lymphocyte; Fungi Imperfecti; Experimental study; In vitro; Thallophyta
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI116354

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.