Naslov
Molecular mechanisms of cell mediated cytotoxicity in early pregnancy

Autori
Rukavina, Daniel ; Laškarin, Gordana ; Bedenicki, Ivica ; Gudelj, Lea ; Podack, Eckhard R.

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

Izvornik
Abstract book / - Žďár nad Sázavou, 1997

Skup
Pozvano predavanje: 3. Symposium of Czech Society for Reproductive Immunology, with International participation

Mjesto i datum
Žďár nad Sázavou, Češka Republika, 29.05.1997. - 01.06.1997

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Perforin; CTL; NK; dLGL; CD56; CD16; Pregnancy

Sažetak
Cytolytic lymphocytes (CL) with the potential of both antigen specific and MHC restricted killing (CTL) and MHC non-restricted killing (NK cells) are present in the pregnancy decidua in the vicinity of the feto-placental unit (FPU), in both human and murine pregnancies. Decidual CL (DL) is endowed with cytolytic molecule perforin (P) in quantities much higher than CL in the peripheral blood (PB). In the first trimester pregnancy CD8+DL are either CD3+CD8bright CD56-P- or CD3-CD8dim CD56+P+ and very few are CD3+CD8+P+ (classical CTL). The level of CD3zeta expression were significantly lower in decidual than PB T cells assessed by mean fluorescence intensity, what suggests that human decidual T cells have differently downregulated CD3 zeta which may compromise their capacity for activation. In the PBL the percentages of P+ cells were higher in term pregnancy (TP) than in the first trimester of pregnancy (FTP), but the most profound changes were found for CD16+P+ cells, i.e. almost the absence in the FTP and high levels at TP. In the FTP peripheral blood P+ cells have prevalent phenotype PCD56bright CD16- (the phenotype of decidual cells) and at TP P+CD56dim CD16+ (phenotype of the non-pregnant females). Cloned CD3- decidual cell populations contained P and serine esterases and retain the overall antigenic phenotype of freshly isolated decidual NK like cells. It is interesting that less molecules related to MHC restricted control of NK cytotoxicity (KIR) are found on decidual than PB CD3- clones. Perforin is not necessary for normal reproduction, since P deficient mice breed well. This is explained by the effects of other molecules mediating CMC (FasL-Fas). Female combined cytotoxicity double deficient mice (Perforin and Fas-L deficiency) develop extensive lymphocytic infiltration of the genital tract and do not reproduce. However, littermates differing only in the presence of a single perforin allele are healthy, breed well and show little infiltration. The role of P is important in the control of adherent cells i.e. in the control of the afferent arch of the immune response (the termination of lymphoproliferation via control of antigen presentation). Furthermore stimuli from decidual adherent cells could be important locally in the regulation of perforin mRNA and protein expression. Both the percentage of P+ cells and mean fluorescence intensity, as a measure of P content/cell, decreased profoundly during 18 hours incubation of PBL. These changes could not be prevented by stimulating PBL with substances known to up-regulate P expression. However, decidual adherent cells, cocultivated in vitro, prevent decrease of P expression in the PB nonadherent cells from nonpregnant females and first trimester pregnancy, as well as decidual lymphocytes.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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