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Despite large‐scale T cell activation, only a minor subset of T cells responding in vitro to Actinobacillus actinomycetemcomitans differentiate into effector T cells
Author(s) -
Zadeh Homayoun H.,
Tanavoli Sara,
Haines David D.,
Kreutzer Donald L.
Publication year - 2000
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2000.035003127.x
Subject(s) - actinobacillus , effector , in vitro , microbiology and biotechnology , chemistry , immunology , biology , periodontitis , medicine , dentistry , biochemistry
Recent studies in our laboratory have demonstrated that Actinobacillus actinomycetemcomitans has a potent T cell stimulatory effect, activating more than half of all T cells. However, since the fate of these activated T cells was not known, the present study sought to determine whether all of these T cells differentiate into effector cells. To that end, the intracellular expression of T cell cytokines (IL‐2, IFN‐γ, IL‐4 and IL‐10) in response to A. actinomycetemcomitans was determined by flow cytometry. Results demonstrated a time‐dependent increase in the expression of the cytokines, most reaching peak levels at 24–48 h. At 48 h, the proportion of T cells expressing each of the cytokines were as follows: IL‐2 (1.7%±0.3), IFN‐γ(1.8%±0.5), IL‐4 (1.0%±0.2) and IL‐10 (1.5%±0.5). These data indicated that only 2–5% of all T cells stimulated with A. actinomycetemcomitans expressed any T cell cytokines. The finding of large‐scale T cell activation in the absence of cytokine expression suggests that the activation of T cells in response to A. actinomycetemcomitans is incomplete. To investigate this phenomenon, peripheral blood mononuclear cells (PBMC) were cultured with A. actinomycetemcomitans for 24 h followed by sorting of the activated (CD69 + ) cells by immunomagnetic separation and restimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. Results demonstrated that nearly 90% of the T cells were unresponsive to further restimulation. A possible explanation for this unresponsiveness is the induction of clonal anergy among the responding T cells. To determine possible preferential effects of the stimulation on specific cytokines, the expression of each cytokine among T cells responding to A. actinomycetemcomitans was compared to the maximum levels achieved by PMA+ionomycin stimulation. Results showed that number of IL‐2 + and IFN‐γ + T cells observed in response to A. actinomycetemcomitans were between 2% and 7% of those seen in response to PMA+ionomycin. Conversely, the proportions of T cells expressing IL‐4 or IL‐10 were between 35% and 90% of those following stimulation with PMA+ionomycin. Hence, A. actinomycetemcomitans appears to more preferentially induce T cells