Appearance and Maturation of T-Cell Subsets During Rat Thymus Ontogeny
Appearance and Maturation of T-Cell Subsets During Rat Thymus Ontogeny
A. VICENTE 0 1
A. VARAS 0 1
R.S ACEDON 0 1
E. JIMINEZ 0 1
J. J. MUlqOZ 0 1
A. G. ZAPATA 0 1
0 aDepartment of Cell Biology, Faculty of Biology, Complutense University , 28040 Madrid , Spain
1 Classification Categories Abbreviations used: DN , CD4-CD8-DP, CD4
2 CD8-F , fetalP, postnatalAD, adult
In previous papers, we have described the ontogenetical development of thymic stromal-cell components (epithelium, macrophages, dendritic cells) of Wistar rats. Here, we correlate those results with the maturation of rat T-cell precursors along the fetal and postnatal life. First T-cell precursors, which colonize the thymus anlage around days 13-14 of gestation, largely express CD45, CD43, CD53, and Thy cell markers, and in a lesser proportion the OX22 antigen. Rat CD3-CD4-CD8- thymocytes present in the earliest stages of gestation could be subdivided in three major cell subpopulations according to the CD44 and CD25 expression: CD44-/+CD25 CD44+CD25 CD44+CD25 On fetal days 17-18, a certain proportion of CD4-CD8cells weakly,express the TcR/3 chain, in correlation with the appearance of the first immature CD4-CD8 thymocytes. This cell subpopulation, in progress to the CD4+CD8 stage, upregulates CD8ce before the CD8/3 chain, expresses the CD53 antigen, and exhibits a high proliferative rate. First mature thymocytes arising from the DP (CD4+CD8+) cells appear on fetal days 20-21. Then, the CD4+:CD8 cell ratio is -<1 changing to adult values (2-3) just after birth. Also, the percentage of V/3TcR repertoire covered in adult thymus is reached during the postnatal period, being lower during the fetal life. Finally, in correlation with the beginning of thymocyte emigration to the periphery a new wave of T-cell maturation apparently occurs in the perinatal rat thymus.
Ontogeny; rat thymus; T-cell development
INTRODUCTION
colonize the organ early during ontogeny. The rat
thymic primordium is colonized around fetal day 14
The development of the thymus gland is governed by
by cell progenitors, the phenotype of which has not
mutual influences between the cell components of
been clearly established although the expression on
thymic stroma and lymphoid-cell progenitors that
them of different cell markers has been reported
(Ritter et al., 1978; Paterson and Williams, 1987;
Kampinga and Aspinall, 1990; Crook and Hunt,
1996)
. Moreover, the existence, as reported in mice
(Godfrey et al., 1993), of cell subpopulations defined
by the expression of CD44 and CD25 in the DN-cell
compartment of rats is controversial. CD44, a
molecule involved in the homing of cell precursors to
mouse thymus has not been described in the rat
thymic progenitors and the CD25 expression reported
early in ontogeny throughout thymic parenchyma
(Habu et al., 1985; Brocke et al., 1987)
and, after
birth, in the thymic medulla
(Habu et al., 1985;
Brocke et al., 1987; Kampinga and Aspinall, 1990)
have not been associated with DN thymocytes,
although IL-2-induced proliferation of rat DN cells
has recently been reported
(Gotlieb et al., 1993)
.
The transition from DN-cell compartment to DP
cell in Wistar rats is marked by the expression of the
CD8 molecule, which allows an intermediate highly
proliferative CD8+CD4 population
(Paterson and
Williams, 1987)
, which in adult rats seems to weakly
express the TcRcq3
(Hfinig et al., 1989a, 1989b)
. On
the other hand, the appearance of mature SP
(CD4-CD8 and CD4+CD8 -) thymocytes around
birth involves changes in the expression of some cell
markers, such as CD45R
(Kampinga and Aspinall,
1990)
and Thy
(Hosseinzadeh and Goldschneider,
1993)
, which could be related to the emigration of
first T lymphocytes to the periphery. Two other
relevant events occur in the rat thymus during the
perinatal period. As previously reported in mice, there
is an important increase of thymic cellularity that
could be associated with in situ increased
proliferation
(Ceredig, 1990; Lawetzky et al., 1991)
and/or
with the arrival at the organ of a second wave of
Tcell precursors (Penit and Vasseur, 1989). In addition,
the CD4/CD8 cell ratio gradually changes during
perinatal life to the adult condition. In mice, this
phenomenon has been correlated with a distinct
capability of the embryonic and adult T-cell
precursors to differentiate
(Adkins, 1991)
and with the
existence of different mechanisms of thymic selection
in each period due to the presence or absence of TdT
activity in adult or fetal precursor cells, respectively
(Shortman and Wu, 1996)
.
Despite this available evidence, a systematic
analysis of the ontogenetical maturation of both the
lymphoid and nonlymphoid cell populations of rat
thymus is, to our knowledge, lacking, although
Kampinga and Aspinall (1990)
carried out an
immunohistochemical study on rat thymus ontogeny and
Htnig et al. (1989a) analyzed by flow cytometry the
expression of some rat T-cell markers, including
CD2, TcRcq3, and CD25 (...truncated)