THE ROLE OF REGULATORYT LYMPHOCYTES IN IMMUNE CONTROL OF MC-2 FIBROSARCOMA/ULOGA REGULATORNIH T LIMFOCITA U IMUNOSNOJ KONTROLI MC-2 FIBROSARKOMA

• Published in: Acta clinica Croatica (Tisak) Vol. 59; no. 2; p. 351
• Main Authors: Jukic, Tomislav, Ma, Ivankovic, Sinisa, Antica, Mariastefania, Jukic, Doroteja Pavan, Rotim, Cecilija, Jurin, Mislav
• Format: Journal Article
• Language: English
• Published: Klinicki bolnicki centar Sestre milosrdnice 01.06.2020
• Subjects: Care and treatment; Development and progression; Fibrosarcoma; Health aspects; Immune response; Lymphocytes; Observations; Croatia
• ISSN: 0353-9466; 1333-9451
• DOI: 10.20471/acc.2020.59.02.20

The role of T regulatory lymphocytes ([T.sub.reg]) particularly in cancer is well known. The goal of the present study was to determine the contribution of these lymphocytes in the regulation of anti-tumor immunity of CBA/HZgr mice against MC-2 fibrosarcoma (4th generation of methylcholanthrene induced tumor). The levels of T lymphocytes (CD4+, CD8+ and CD4+CD2S+) were determined 8 and 20 days after tumor transplantation. Further, the role of CD4+CD2S+ ([T.sub.regs]) in tumor-host interaction was evaluated in vitro and in vivo by using specific monoclonal antibodies. We found that splenocytes of both control and [T.sub.reg] depleted tumor bearing mice strongly but differently inhibited growth of tumor cells in vitro. While splenocytes of untreated mice exhibited significant decrease of this activity (from 74.4% to 62.6% and 32.95%), the splenocytes of [T.sub.reg] depleted mice showed increase of this activity (from 79.5% to 84.3% and 86.2%) from day 6 to day 13 and day 21 after tumor grafting, respectively. Further, upon i.v. injecting specific monoclonal anti-[T.sub.reg] antibody tumor immediately prior to tumor cell intracutaneous transplantation, the tumor was rejected after initial growth. In treated mice, the incidence of [T.sub.reg] cells was very low initially, reaching normal values two weeks later. These animals were shown to be resistant to tumor transplantation four months later. Key words: Regulatory T lymphocytes; Tumor growth; Specific monoclonal antibodies; Experimental mice Uloga T regulatornih limfocita dobro je poznata, osobito kod tumora. Cilj ovoga istraživanja bio je utvrditi doprinos ovili limfocita u regulaciji antitumorske imunosti CBA/HZgr miševa protiv MC-2 fibrosarkoma (4. generacija metilkolantrenom izazvanog tumora). Razine T limfocita (CD4+, CD8+ and CD4+CD25+) odredivale su se 8 i 20 dana nakon transplantacije tumora. Nadalje, uloga CD4+CD25+ T limfocita ([T.sub.reg] ) u interakciji tumora i domacina procijenjena je in vitro i in vivo primjenom specificnih monoklonskih protutijela. Utvrdili smo da splenociti kako kontrolnih miševa tako i miševa s tumorom bez [T.sub.reg] snažno, ali razlicito suzbijaju rast tumorskih stanica in vitro. Dok su splenociti netretiranih miševa pokazivali znacajno smanjenje ove aktivnosti (sa 74,4% na 62,6% i 32,95%), splenociti miševa bez [T.sub.reg] pokazivali su porast ove aktivnosti (sa 79,5% na 84,3% i 86,2%) od 6. do 13. i 21. dana nakon transplantacije tumora. Uz to, nakon i.v. injektiranja specificnog monoklonskog anti-[T.sub.reg] tumorskog protutijela neposredno prije intrakutane transplantacije tumorskih stanica, nakon pocetkog rasta nastupilo je odbacivanje tumora. Kod tretiranih miseva incidencija [T.sub.reg] stanica bila u pocetku vrlo niska i dostigla je normalne vrijednosti dva tjedna kasnije. Nakon cetiri mjeseca pokazalo se da su ove životinje otporne na transplantaciju tumora. Kljucne rijeci: Regulatorni T limfociti; Tumorski rast; Specificna monoMonska protutijela; Eksperimentalni miševi