Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings

Abstract

Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T-cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-y) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN--y secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF-a) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-at was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-a response and the negative IL-4 finding may speak for the importance of the Thl-like pattern in immunity to F. tularensis. * Corresponding author. sponses, and in another nine subjects blood lymphocyte subpopulations were studied during the 14 days after vaccination.of antigenand mitogen-induced human T lymphocyte proliferation by tumor necrosis factor-a.

Development of Francisella tularensis antigen responses measured as T-lymphocyte proliferation and cytokine production (tumor necrosis factor alpha, gamma interferon, and interleukin-2 and -4) during human tularemia

“…The present results demonstrated that TNF-ot was produced by FT-Ag-stimulated PBMC early in tularemia before any IFN-y was measurable. TNF-ot responses in cases of natural infection seemed to differ from those induced by a live attenuated F. tularensis vaccine strain, when TNF-a secretion was found after the appearances of positive FT-Ag LBT and IFN-y responses (6). We consider the difference quantitative, caused by the ability of the wild-type F. tularensis strain to survive longer in phagocytes (8).…”

Interleukin-12 in infectious diseases

“…tularensis. In a murine model of Francisella tularensis infection, development of protective immunity to challenge with an attenuated live vaccine strain (LVS) depends on stimulation of specific IFN-␥-producing T cells (199,387). Both T-dependent and T-independent host immune mechanisms contribute to the generation of immunity to F. tularensis (76,101), with cytokines such as IFN-␥ playing an important role in the activation of microbicidal macrophages (121,234).…”

Vaccine-Mediated Mechanisms Controlling Replication of Francisella tularensis in Human Peripheral Blood Mononuclear Cells Using a Co-culture System

“…A number of studies have characterized the human memory immune responses resulting from tularemia or tularemia vaccination (Tärnvik et al, 1985 ; Tärnvik, 1989 ; Karttunen et al, 1991 ; Surcel et al, 1991 ; Sjöstedt et al, 1992 ; Ericsson et al, 1994 ; Eneslätt et al, 2011 , 2012 ). In accordance with the intracellular nature of the pathogen, most evidence indicates that cell-mediated immunity (CMI) is the predominant factor contributing to the protective efficacy of the tularemia vaccine (Tärnvik, 1989 ).…”