Correlation between phenotypic characteristics of mononuclear cells isolated from human periapical lesions and their in vitro production of Th1 and Th2 cytokines.
The development and progression of periapical dental lesions, mediated by the specific immune response, are poorly understood. In these processes, an interplay of different proinflammatory and immunoregulatory cytokines is of crucial importance.


OBJECTIVE
To examine the activation of T helper 1 (Th1) and Th2 immune responses in 25 human periapical lesions based on the ex vivo production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by mononuclear cells (PL-MNC).


METHODS
The levels of IFN-gamma and IL-4 in culture supernatants of PL-MNC, determined by ELISA, were correlated with concentrations of these cytokines in cultures of control MNC from peripheral blood (PB-MNC), cellular composition of inflammatory cells and phenotypic characteristics of PL-MNC.


RESULTS
We detected high levels of IFN-gamma in all samples, after cell stimulation with phorbol myristate acetate and Ca(2+) ionophore, that were not statistically different from the levels of IFN-gamma in PB-MNC cultures. IL-4 was detected in 76% samples, but its concentrations were much lower than in PB-MNC samples. The levels of IFN-gamma were higher in cultures of PL-MNC isolated from periapical lesions with predominance of T cells (T-type lesions) and correlated positively with the proportion of antigen-presenting cells (macrophages and dendritic cells), CD4(+) T cells and IgG2(+) B cells/plasma cells. The levels of IL-4 correlated negatively with the proportion of macrophages, but positively with the number of mast cells and IgG4(+) cells. IL-18Ralpha, a stable marker of Th1 cells, was detected on a relatively small proportion of CD3(+) T cells and its expression correlated with the levels of IFN-gamma. However, the expression of ST2L, a stable Th2 cell marker, was not detected. The levels of Th1 and Th2 cytokines did not correlate with clinical characteristics of the lesions, defined by the presence of symptoms.


CONCLUSIONS
Cumulatively, our results suggest the predominance of Th1 immune response in periapical lesions.
Colić
Miodrag
M
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia and Montenegro. vmaimi@EUnet.yu
Lukić
Aleksandra
A
Vucević
Dragana
D
Milosavljević
Petar
P
Majstorović
Ivana
I
Marjanović
Marjan
M
Dimitrijević
Jovan
J
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014076:Tooth Diseases / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma