High frequency of spontaneous interferon-gamma-producing cells in human tonsils: role of local accessory cells and soluble factors

Abstract

SUMMARYThe frequency of mononuclear cells (MNC) spontaneously secreting interferon-gamma (IFN-y) has been examined in freshly isolated cell suspensions from human palatine tonsils. Two-site reverse enzyme-linked immunospol (ELISPOT) analyses, involving short term (20 h) incubation of MNC in the absence of any added exogenous stimulus, revealed that tonsillar MNC suspensions contain exceptionally large numbers ofcells secreting IFN-y. No significant differences were observed when comparing the frequency of IFN-y-producing cells between cell suspensions obtained from hyperplastic and tonsillitis specimens. Cell-sorting experiments disclosed that spontaneous tonsiltar IFN-y production was essentially contributed by CD4"' T cells, and required the presence of accessory cells and/or soluble factors to be detected. Thus, depletion of plastic adherent cells or monocytes from the tonsillar MNC suspensions resulted in reduced numbers of detectable IFN-ysecreting cells. Addition of very small numbers of autologous monoey tes restored spontaneous I FN-y production in tonsillar MNC cultures depleted of monocytes. Neutralization of endogenous IL-l/J and IL-2. as well as blocking of the IL-2 receptor, also decreased IFN-y production from un fractionated tonsillar cells. Addition of exogenous IL-l/i restored IFN--; production in cultures of tonsillar MNC depleted of plastic adherent cells. Furthermore. IL-l/f synergized with lL-2 by increasing intracellular as well as cell-free levels of IFN-y in cultures of unfraclionatcd tonsillar MNC. This study further establishes that the tonsils are highly active immunologieal organs containing large numbers of T cells spontaneously producing lFN-y whose detection is contingent upon the presence of functional accessory cells. It also demonstrates that concomitant production of IL-1/? and IL-2 occurs in tonsils and is necessary to maintain ongoing synthesis and extracellular aecumulation of IFN-y in these organs.

Immunohistochemical detection of co-localizing cytokine and antibody producing cells in the extrafollicular area of human palatine tonsils

“…In contrast, a high frequency oi' IFN--/-producing cells were observed in the extrafollicular area. This is in agreement with in n/m experiments showing a high production of IFN-y in freshly isolated tonsillar cell suspensions [35] and tonsillar lymphocytes stimulated with PHA or Sendai virus [36.37]. Moreover, allogeneic stimulation of BALB/c (H-2'') mouse splenic T cells with CBA/Ca (H-2'') mouse dendritic cells or FcR' macrophages generated elevated levels of IFN-y detectable throughout the 7-day culture period.…”

Feasibility and Diagnostic Utility of Antigen-Specific Interferon-γ Responses for Rapid Immunodiagnosis of Tuberculosis Using Induced Sputum

“…Increasing the length of mixing time after addition of DTT failed to improve sample quality. Moreover, previous studies [8] , [18] , [19] suggest a high degree of spontaneous IFN-γ release by mononuclear cells, in the absence of any exogenous stimuli, especially those compartmentalized to the lungs of patients. Finally, several steps were taken to minimise cellular and other debris.…”

The association of sore throat and psoriasis might be explained by histologically distinctive tonsils and increased expression of skin-homing molecules by tonsil T cells

“…6), suggesting a potential Th17 cytokine bias. A number of studies have shown increased expression of cytokines by T cells from RT compared with HT tonsils, with a predominance of Th1 over Th2 cytokines [43][44][45]. When cells from HT and RT tonsils were stimulated with intact, heat-inactivated Haemophilus influenzae and Group A Streptococcus, H. influenza induced IL-1α, IL-1β, tumour necrosis factor (TNF)-α, IL-6, IL-8, IL-2, interferon (IFN)-γ, TNF-β and IL-10 production in both tonsil groups, but Group A Streptococcus induced significantly higher frequencies of IFN-γ-positive cells in the RT group [46].…”