Naslov
Modulatory effects of SMS 201-995 on processes of T-cell proliferation and differentiation

Autori
Trobonjača, Zlatko ; Radošević-Stašić, Biserka ; Rukavina, Daniel

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Effector functions of immune cells / European Federation of Immunological Societies (EFIS) and Croatian Imunological Society - : Hrvatsko imunološko društvo, 1998, 8-8

Skup
John Humphrey Course

Mjesto i datum
Dubrovnik, Hrvatska, 11.10.1998. - 14.10.1998

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
SMS 201-995; thymus; dexamethasone; apoptosis

Sažetak
Activation of immature thymocytes via TCR as well as exposure to glucocorticoids, such as dexamethasone, results in apoptosis. In vivo administration of anti-CD3 antibodies to mice induces programmed cell death predominantly in double positive (CD4+CD8+), CD3low cortical and CD3intermediate medullar cell subset, that is analogous to the antigen-induced negative selection of thymocytes, capable of recognizing self antigens. The main event in negative selection process is TCR-CD3 occupancy via TCR-MHC complex interactions, that leads to the clonal deletion. This process is additionally regulated through different intercellular contacts and humoral factors. Since the expression of the somatostatin gene mRNA was found in thymus epithelial cells, in the present study we investigated the influences of somatostatin analogue SMS 201-995 on: 1) apoptosis induced in vivo and in vitro by anti-CD3 antibodies or by dexamethasone, 2) on the maturation process of normal thymocytes in vitro and 3) on the growth of Yac-1, T-cells line in vitro. For this purpose the phenotypic analysis of CD4/8, TCR, CD54 and CD44 marker expression, as well as nucleic fragmentation of thymocytes were estimated 6, 18, 24, 36 and 72 hours after the treatment with anti-CD3 antibodies (2 mg/ml) or dexamethasone (1 mg/ml) in the presence of SMS (0,1 mg/ml). Thymocyte phenotype was determined by direct and indirect immunofluorescence technique. Percentage of apoptotic cells was calculated by cell cycle analysis on the flow cytometer in the region of "sub-G1" peak, while apoptotic DNA degradation was proved by gel electrophoresis technique. The data have shown that SMS downregulated the apoptotic process, induced by anti-CD3 antibodies, but did not affect the dexamethasone-induced cell death. SMS changed also the phenotype of nonapoptotic cells, indicating its influence on the processes of thymocyte maturation and clonal deletion of self-reactive cells.

Izvorni jezik
Engleski

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