IL-12 in conjunction with dendritic cells enhances antiviral CD8+ CTL responses in vitro

被引:84
作者
Bhardwaj, N
Seder, RA
Reddy, A
Feldman, MV
机构
[1] HOSP SPECIAL SURG,NEW YORK,NY 10021
[2] NIH,BETHESDA,MD 20892
关键词
dendritic cells; cytolytic T cells; CD8+ T cells; interleukin; 12; vaccines;
D O I
10.1172/JCI118843
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
CD8+ cytolytic T lymphocytes (CTLs) are important mediators for resistance to infections and malignant diseases. IL-12 enhances proliferative and cytolytic responses by killer cells, but its function in the generation of human antiviral CD8+ T cell responses has not been defined. We therefore evaluated the role of IL-12 in the generation of CTLs to influenza-infected dendritic cells. IL-12 was not detectable in supernatants of infected-dendritic cells, or during CTL generation. Furthermore, anti-IL-12 antibody did not block CTL generation. However, exogenous IL-12 (30-300 pg/ml) enhanced CD8+ T cell proliferative and cytolytic responses. The effect was greatest in individuals with weak reactivity to influenza virus or at antigen-presenting cell (APC):T cell ratios of 1:100 or less. IL-12 augmented interferon-gamma production during CTL generation. The CTL enhancing effects of the cytokine, however, could not be blocked by neutralizing anti-interferon-gamma antibody. Together with IL-12, antigen-pulsed dendritic cells may be a useful approach for boosting CTL responses against infectious agents and malignancies.
引用
收藏
页码:715 / 722
页数:8
相关论文
共 43 条
[1]   INACTIVATED INFLUENZA-VIRUS, WHEN PRESENTED ON DENDRITIC CELLS, ELICITS HUMAN CD8(+) CYTOLYTIC T-CELL RESPONSES [J].
BENDER, A ;
BUI, LK ;
FELDMAN, MAV ;
LARSSON, M ;
BHARDWAJ, N .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :1663-1671
[2]   INFLUENZA VIRUS-INFECTED DENDRITIC CELLS STIMULATE STRONG PROLIFERATIVE AND CYTOLYTIC RESPONSES FROM HUMAN CD8+ T-CELLS [J].
BHARDWAJ, N ;
BENDER, A ;
GONZALEZ, N ;
BUI, LK ;
GARRETT, MC ;
STEINMAN, RM .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (02) :797-807
[3]  
BLOOM ET, 1994, J IMMUNOL, V152, P4242
[4]   INTERLEUKIN (IL)-15 IS A NOVEL CYTOKINE THAT ACTIVATES HUMAN NATURAL-KILLER-CELLS VIA COMPONENTS OF THE IL-2 RECEPTOR [J].
CARSON, WE ;
GIRI, JG ;
LINDEMANN, MJ ;
LINETT, ML ;
AHDIEH, M ;
PAXTON, R ;
ANDERSON, D ;
EISENMANN, J ;
GRABSTEIN, K ;
CALIGIURI, MA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (04) :1395-1403
[5]   INDUCTION OF ANTITUMOR CYTOTOXIC T-LYMPHOCYTES IN NORMAL HUMANS USING PRIMARY CULTURES AND SYNTHETIC PEPTIDE EPITOPES [J].
CELIS, E ;
TSAI, V ;
CRIMI, C ;
DEMARS, R ;
WENTWORTH, PA ;
CHESNUT, RW ;
GREY, HM ;
SETTE, A ;
SERRA, HM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (06) :2105-2109
[6]   Peptide-pulsed dendritic cells induce antigen-specific, CTL-mediated protective tumor immunity [J].
Celluzzi, CM ;
Mayordomo, JI ;
Storkus, WJ ;
Lotze, MT ;
Falo, LD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (01) :283-287
[7]   INDUCTION OF INTERFERON-GAMMA PRODUCTION BY NATURAL-KILLER-CELL STIMULATORY FACTOR - CHARACTERIZATION OF THE RESPONDER CELLS AND SYNERGY WITH OTHER INDUCERS [J].
CHAN, SH ;
PERUSSIA, B ;
GUPTA, JW ;
KOBAYASHI, M ;
POSPISIL, M ;
YOUNG, HW ;
WOLF, SF ;
YOUNG, D ;
CLARK, SC ;
TRINCHIERI, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (04) :869-879
[8]   ENHANCING EFFECT OF NATURAL-KILLER-CELL STIMULATORY FACTOR (NKSF/INTERLEUKIN-12) ON CELL-MEDIATED CYTOTOXICITY AGAINST TUMOR-DERIVED AND VIRUS-INFECTED CELLS [J].
CHEHIMI, J ;
VALIANTE, NM ;
DANDREA, A ;
RENGARAJU, M ;
ROSADO, Z ;
KOBAYASHI, M ;
PERUSSIA, B ;
WOLF, SF ;
STARR, SE ;
TRINCHIERI, G .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (08) :1826-1830
[9]   IMPAIRED INTERLEUKIN-12 PRODUCTION IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS [J].
CHEHIMI, J ;
STARR, SE ;
FRANK, I ;
DANDREA, A ;
MA, XJ ;
MACGREGOR, RR ;
SENNELIER, J ;
TRINCHIERI, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (04) :1361-1366
[10]   INTERLEUKIN-12 INDUCES THE DIFFERENTIATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I-PRIMED CYTOTOXIC T-LYMPHOCYTE PRECURSORS INTO ALLOSPECIFIC CYTOTOXIC EFFECTORS [J].
CHOUAIB, S ;
CHEHIMI, J ;
BANI, L ;
GENETET, N ;
TURSZ, T ;
GAY, F ;
TRINCHIERI, G ;
MAMICHOUAIB, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (26) :12659-12663