Citokinski profil limfocita T iz krvi i bronhoalveolarnog ispirka u bolesnika s plućnom tuberkulozom [ Cytokine profile of T-lymphocytes from peripheral blood and bronchoalveolar lavage fluid in patients with active pulmonary tuberculosis ]

Boras, Zagorka (2004) Citokinski profil limfocita T iz krvi i bronhoalveolarnog ispirka u bolesnika s plućnom tuberkulozom [ Cytokine profile of T-lymphocytes from peripheral blood and bronchoalveolar lavage fluid in patients with active pulmonary tuberculosis ]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Cell-mediated immunity, especially from CD4+ T-lymphocyte function, plays an important role in eliminatig mycobacteria in tuberculosis. Reports on Th1-type and Th2-type cytokines in human tuberculosis are conflicting, and little is known about their role in tissue damage. We examined the cytokine responses of CD4+ and CD8+ T-lymphocytes in peripheral blood and bronchoalveolar lavage fluid (BAL) from 20 purified protein derivative skin-positive (PPD+) and from nine PPD skin-negative patients with active pulmonary tuberculosis. Parallel blood and BAL fluid samples from each subject were shortly incubated with or without PMA and ionomycin, and the proportions of CD4+ and CD8+ T-lymphocytes producing interferon- (IFN-) or interleukin-4 (IL-4) were measured by flow cytometry. There was no age or BMI difference of examiness between PPD+ and PPD- group. PPD- patients, in relation to PPD+ patients, had a significant higher percent of CD4+ T-lymphocytes in the BAL. No significant difference was found between groups in percent CD4+ T-lymphocytes in peripheral blood and CD8+ T-lyphocytes peripheral blood and BAL. At the same time, PPD- patients have shown a significant higher percent of CD4+ T-lymphocytes which produced IFN- in relation to the entire number activated CD4+ T-lymphocytes in a peripheral blood. No significant difference was found in the production IFN- of CD8+ T-lymphocytes peripheral blood and BAL and CD4+ T-lymphocytes in the BAL. CD4+ T-lymphocytes of peripheral blood in two PPD-patients produced IL-4 while the rest of the T-lymphocytes peripheral blood and BAL suppressed the production of this cytokine. Among PPD+ patients group we have found a higher percent of CD4+ as well as CD8+ T-lymphocytes which produce IFN- in BAL in relation to the peripheral blood, while the BAL in PPD- group was more active only in CD4+ production IFN-. These results suggest a higher immune activity in the blood of PPD- patients while the BAL is more active in both groups of examinees in relation to the peripheral blood. It suggests that the separation of T-lymphocytes, specially those producing IFN- from peripheral blood to the lungs, occurs in tuberculosis.

Abstract in Croatian

Stanicama je posredovana imunost, naročito CD4+ T-limfocitima, ključna u eliminaciji mikobakterija u tuberkulozi. Dosadašnja saznanja o Th1 i Th2 tipu citokinske proizvodnje u ljudskoj tuberkulozi konfliktna su i malo se zna o njihovoj ulozi u tkivnom oštećenju. Mi smo istraživali citokinski odgovor CD4+ i CD8+ T-limfocita periferne krvi i BAL-a u 20 PPD+ i devet PPD- bolesnika s aktivnom plućnom tuberkulozom. Uzorci periferne krvi i BAL-a svakog bolesnika bili su kratkotrajno inkubirani s PMA i ionomicinom ili bez njih, nakon čega smo na protočnom citometru određivali CD4+ i CD8+ T-limfocite koji su proizvodili IFN- ili IL-4. Između PPD+ i PPD- skupine nije bilo razlike u dobi ispitanika i BMI. PPD- bolesnici su, u odnosu na PPD +, imali značajno veći postotak CD4+ T-limfocita u BAL-u. Nije bilo značajnije razlike među grupama u postotku CD4 T-limfocita u perifernoj krvi i CD8+ u perifernoj krvi i BAL-u. Istovremeno, PPD- bolesnici iskazali su značajno veći postotak CD4+ T-limfocita u perifernoj krvi koji su proizvodili IFN-, a u odnosu na sveukupni broj tih aktiviranih CD4+ T-limfocita. Nije bilo razlike između skupina u proizvodnji IFN- od CD8+ T-limfocita krvi i BAL-a i CD4+ T-limfocita BAL-a. CD4+ T-limfociti periferne krvi dva PPD- bolesnika su proizvodili IL-4, a ostali su T-limfociti periferne krvi i BAL-a zakazali u proizvodnji navedenog citokina. Unutar PPD+ skupine bolesnika našli smo značajno veći postotak i CD4+ i CD8+ T-limfocita koji proizvode IFN- u BAL-u u odnosu na perifernu krv, dok je u PPD- skupine BAL bio aktivniji samo u CD4+ proizvodnji IFN-. Ovakvi rezultati sugeriraju veću imunološku aktivnost u PPD- bolesnika u krvi, a BAL je obje skupine ispitanika aktivniji u odnosu na perifernu krv. Sve to sugerira da u tuberkulozi dolazi do odjeljivanja T-limfocita, naročito onih koji proizvode IFN-, iz periferne krvi u pluća.

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