Enhanced and prolonged efficacy of superantigen-induced cytotoxic T lymphocyte activity by interleukin-2 in vivo.
The bacterial superantigen, staphylococcal enterotoxin A (SEA) activates T cells with high frequency and directs them to lyse MHC-class-II-expressing cells in superantigen-dependent cell-mediated cytotoxicity (SDCC). Treatment of mice with SEA induced strong CD8+ T-cell(CTL)-mediated SDCC, as well as abundant cytokine production from CD4+ and CD8+ T cells. However, both cytotoxicity and cytokine release were transient. In contrast, combined treatment with SEA and recombinant interleukin-2 (rIL-2) increased peak levels and maintained CTL activity. These effects were concomitant with an increased number of SEA-reactive V beta 11+ T cells. Both the CD4+ and CD8+ populations contained higher frequencies of cells expressing IL-2 receptor (IL-2R) alpha beta, which suggests that continuous IL-2R signaling preserves its high expression and subsequently prevents loss of growth factor signals necessary for expansion of T cells. Although IL-2R expression was increased among both CD4+ and CD8+ cells, only the cytotoxic function of CTL, but not cytokine production from either CD4 or CD8, was augmented. These findings demonstrate that treatment with rIL-2 potentiates superantigen-induced cytotoxicity and maintains high CTL activity. rIL-2 might therefore be useful in improving superantigen-based tumor therapy.
Belfrage
H
H
Department of Tumor Immunology, Wallenberg Laboratory, Lund University, Sweden.
Dohlsten
M
M
Hedlund
G
G
Kalland
T
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology; D018089:Superantigens / Q000276:immunology* / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*
D004768:Enterotoxins; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma