Fetal T-Lymphocyte Subpopulations in Normal Pregnancies

Thilaganathan, B.; Mansur, Carlos A.; Morgan, G.; Nicolaides, Kypros H.

doi:10.1159/000263651

Cited by 43 publications

(26 citation statements)

References 19 publications

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“…A broader analysis of T-cell markers further supports our conclusion that the midgestation fetus contains a notable number of activated T-cells. Although a previous study failed to identify any CD56 þ natural cytotoxic T-cells in the fetus [40], we observed a similar number of CD56 þ T-cells in the fetus as in the adult. About 17% of fetal T-cells expressed the g/d TCR which was higher than in the neonate and adult, consistent with previous findings [41].…”

Section: Discussioncontrasting

confidence: 47%

Ontogenic changes in CD95 expression on human leukocytes: prevalence of T-cells expressing activation markers and identification of CD95−CD45RO+ T-cells in the fetus

Muench

Bartsch

Chen

et al. 2003

Developmental & Comparative Immunology

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The ontogeny of the human immune system was studied by analyzing fetal and adult tissues for the presence of various lymphocytes populations and activation/maturation markers. CD95 (fas) was expressed in hematopoietic tissues during the final stages of development of monocytes, granulocytes, NK cells and T cells, but to a much lesser extent on B cells. In the periphery, CD95 expression declined on granulocytes and NK cells. CD95 was expressed at a higher level on CD45RA þ peripheral T-cells in the fetus than in the adult. Contrary to the belief that most fetal T-cells are naïve or resting, a notable number of CD45RO þ Tcells were observed as well as an unique CD95 2 CD45RO þ population. Activation markers CD25, CD122, CD69 and CD80were also present on fetal T-cells. These findings indicate that in the initial weeks following thymic maturation, a high frequency of T-cells is activated in the periphery of the fetus. q

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Section: Discussioncontrasting

confidence: 47%

Ontogenic changes in CD95 expression on human leukocytes: prevalence of T-cells expressing activation markers and identification of CD95−CD45RO+ T-cells in the fetus

Muench

Bartsch

Chen

et al. 2003

Developmental & Comparative Immunology

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Section: Introductionmentioning

confidence: 99%

“…However, mature T cells are not detected in the thymus before 12 to 13 WGs 38,39 ; they start egressing the thymus and progressively colonize the periphery from about the end of the 13th/begining of the 14th WG, 40,41 with numbers and percentages of CD3 ϩ cells increasing exponentially during gestation. 42 Different subsets of cells with high suppressive activities have already been described in human cord blood 43 : (1) directly suppressive CD8 ϩ CD4 Ϫ cells, 44 (2) CD4 ϩ CD8 Ϫ cells able to induce secondary suppressor cells, 45,46 (3) and CD3 ϩ CD4 Ϫ CD8 Ϫ CD45R ϩ cells able to inhibit IL-2 production. 47 More recently CD8 ϩ CD25 ϩ cells 48 and CD4 ϩ CD25 ϩ49-51 regulatory T cells have been identified in human cord blood or thymus.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses

Darrasse-Jèze

Marodon

Salomon

et al. 2005

Blood

134

113

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Little is known about the ontogeny of naturally occurring CD4 ؉ CD25 ؉ regulatory/suppressor T cells that play a major role in maintaining self-tolerance in mice and humans. In rodents, thymectomy on day 3 of life leads to multiple organspecific autoimmune diseases that can be prevented by adoptive transfer of regulatory T cells, suggesting their neonatal development. We investigated regulatory T-cell ontogeny in 11 human fetuses. Together with the first mature T cells, thymic CD4 ؉ CD25 ؉ cells were detected as early as 13 weeks of gestation. Thymic CD25 ؉ cells appeared to be positively selected at the CD4 ؉ CD8 ؉ CD3 hi differentiation stage, as assessed by CD1a and CD69 expression. The proportion of thymic CD4 ؉ CD25 ؉ cells appeared quite stable with age, around 6% to 7%, similar to the proportion observed in infant thymi. Extrathymic CD4 ؉ CD25 ؉ T cells could hardly be detected at 13 weeks of gestation but were present from week 14 onwards. As adult regulatory T cells, purified CD4 ؉ CD25 ؉ fetal cells were anergic and suppressed T-cell proliferative responses; they expressed intracellular cytotoxic T-lymphocyte-associated antigen 4 (CTLA- 4 IntroductionT cells capable of suppressing immune responses have been hypothesized for a long time. 1 Functional assays have supported their existence 2,3 but the inability to phenotypically identify them has hampered their further study. However, there is now clear evidence that CD4 ϩ cells expressing the interleukin-2 receptor ␣ chain (CD25) contain a population of naturally and ubiquitously present cells endowed with suppressive activities. [4][5][6][7] The lack of a known specific surface marker makes it hard to distinguish CD4 ϩ CD25 ϩ regulatory T cells (Treg's) from CD4 ϩ activated effector T cells, which may transitorily express CD25. 8 As of today, Treg's are best identified by the expression of (1) high levels of CD25 (CD25 hi ), [8][9][10] (2) the forkhead/winged helix transcription factor Foxp3, 11 (3) high levels of intracytoplasmic cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), 12,13 and (4) the glucocorticoid-induced tumor necrosis factor receptor (GITR) surface marker. 14 Since these individual markers are neither specific nor always simultaneously expressed, the authentication of bona fide Treg's relies on the demonstration that (1) they are anergic in vitro in the absence of exogenous IL-2 and (2) they indeed suppress effector T-cell responses.It is now well established that Treg's play a major role in maintenance of self-tolerance and control of autoimmune diseases. 7,15 They are also involved in regulation of T-cell homeostasis [16][17][18] and modulation of immune responses to alloantigens, tumor cells, and various pathogens. [19][20][21][22][23][24][25][26] In the periphery, at steady-state, Treg's represent a stable proportion of the CD4 ϩ T cells, typically 5% to 12% in mice and humans. Although Treg's are anergic in vitro, in vivo studies have shown that some Treg's are quiescent with a long lifespan whereas others divide extensively du...

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“…Information regarding the immunological function in the human fetus is scarce. Morphological studies in man have shown that single positive thymocytes can be detected as early as the 11th-12th week of gestation and that small amounts of mature lymphocytes are seen in peripheral blood at around 14 weeks of gestation [10,11]. These descriptive studies on mature lymphocytes in the fetus do not, however, provide information on immunological function or the capacity of rejection.…”

Section: Introductionmentioning

confidence: 99%

Mixed Lymphocyte Culture of Human Fetal Liver Cells

Lindton¹,

Markling

Ringdén

et al. 2000

Fetal Diagn Ther

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Objective: In order to study the immunological function of the human fetus in the first and second trimesters, mixed lymphocyte culture (MLC) of fetal liver and thymic cells was performed. MLC is a functional test to determine human lymphocyte antigen-D incompatibilities. Methods: Human fetal liver and thymic tissue was obtained from abortions in gestational weeks 7–17.5. Forty-seven fetuses were studied with one-way MLC. The cells were stimulated by adding irradiated fetal liver cells, adult bone marrow and peripheral blood lymphocytes. The activity was measured as DNA incorporation of radiolabeled thymidine. Results: The results indicate that the human fetus is competent to react as early as 11–12 weeks of gestation and in some cases even earlier. In very immature fetal livers (< 8 weeks), the MLC seems to be inhibited. Conclusions: Our data suggest that the human fetus can react against foreign transplantation antigens earlier than previous papers have claimed. The onset of reactivity seems to differ considerably among fetuses. The present findings may explain some of the limited success of in utero transplantations of hematopoietic stem cells in human fetuses of normal immunological status.

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Fetal T-Lymphocyte Subpopulations in Normal Pregnancies

Cited by 43 publications

References 19 publications

Ontogenic changes in CD95 expression on human leukocytes: prevalence of T-cells expressing activation markers and identification of CD95−CD45RO+ T-cells in the fetus

Ontogenic changes in CD95 expression on human leukocytes: prevalence of T-cells expressing activation markers and identification of CD95−CD45RO+ T-cells in the fetus

Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses

Mixed Lymphocyte Culture of Human Fetal Liver Cells

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