In the present study, we have analyzed the appearance and maturation of &#947;/&#948; T cells,recognized with a new mAb V65, in the central and peripheral lymphoid organs of fetal,neonatal, and adult Wistar rats. Cytofluorometrical analysis demonstrated the first V65+&#947;/&#948; T cells in the thymus of 16-17-day embryonic rats, although by immunohistology, theywere identified only in 19-day rat embryos in both the cortico-medullary border and thymicmedulla. Phenotypically, &#947;/&#948; thymocytes from fetal and neonatal thymus expressed CD3,CD2, and CD5, but only 60-80% were CD8+ and approximately 40-50% expressed the &#945;chain (p55) of the IL-2R. In the periphery, the immunohistological study identified for thefirst time ,&#947;/&#948; T cells in the splenic white pulp and the gut of 21-day fetal rats, where theyoccurred within the epithelium as well as in the lamina propria. After birth, &#947;/&#948;lymphocytes appeared in the skin, where they were present as dendritic epidermal T cellsin increasing numbers during postnatal life. Whereas these &#947;/&#948; T cells formed thepredominant T-cell population in the rat skin, &#947;/&#948; T cells in peripheral lymphoid organs,BALT, or the gut only represented a minor T-cell population. These results are discussed incomparison to &#947;/&#948; T cells of other vertebrate species.

P.  K&#252;hnlein

A.  Vicente

A.  Varas

T.  H&#252;nig

A.  Zapata

&#947;/&#948; Cells in Fetal, Neonatal, and Adult RatLymphoid Organs

Control of growth and differentiation during mammalian embryogenesis is regulated by
growth factors from embryonic and/or maternal sources. Cytokines are polypeptide growth
factors that are released by a variety of activated immune and nonimmune cells. To identify
novel members of the cytokine family that could be involved in the growth and
differentiation of the preimplantation embryo, we studied the expression pattern of several
genes encoding cytokines and their receptors during mouse preimplantation development
in vitro We found that poly(A)+ mRNAs for IL-1, IL-3, IL-6, IL-7, and TNFα are
differentially expressed at several stages of mouse preimplantation development, including
unfertilized oocytes. Immunostaining of preimplantation embryos using monoclonal antibodies
specific for several cytokines and their receptors revealed that at least some of these
mRNAs are translated into mature proteins during preimplantation development (IL-1,
IL-6, and TNFα). Positive staining for IL-1 and IL-6 receptors was also detected at these
stages of development. The controlled expression of these “inflammatory-type” cytokines
and their receptors suggests a role for these growth factors during the early phases of mouse
ontogeny.

Nicole Gerwin

Gui-Quan Jia

Robert Kulbacki

José C. Gutierrez-Ramos

Interleukin Gene Expression in Mouse Preimplantation
Development

The presence in the thymus of hemopoietic cells other than thymocytes has been known for
many years, but the extent of the hemopoietic activity of the thymus and the possible
functional implications have only recently begun to receive much attention. This review
summarizes the literature in this field, especially in the light of current cytokine and
thymic-factor knowledge, and includes clinical relevance where possible.

Marion D. Kendall

Hemopoiesis in the Thymus

We have addressed the question whether the epithelial stroma in the thymus is derived
from a common stem cell or whether cortical and medullary epithelial cells are derived from
different embryonic stem cells emerging, for example, from endoderm and ectoderm. By the
use of rapidly expanding cultures of thymic epithelial cells (TEC) from 14 to 16 day-old
murine fetuses and by specific antibodies against cortical and medullary epithelium,
respectively, we were able to demonstrate a small subpopulation of double-labeled TEC in
the cultures. These cells were not present in TEC cultures initiated from thymuses of
neonatal mice. Double-labeled TEC were also found in tissue sections from fetal thymuses.
These findings may indicate that TEC populations of the cortex and the medulla are derived
from a common stem cell, with potential for differentiation toward both cortical and
medullary TEC.

Carsten Röpke

Peter Van Soest

Peter Paul Platenburg

Willem Van Ewijk

A Common Stem Cell for Murine Cortical and Medullary
Thymic Epithelial Cells?

Increasing evidence reveals that extracellular matrix components can be regarded as a group
of mediators in intrathymic T-cell migration and/or differentiation. Yet, little is kown about
the expression and putative function of one particular extracellular matrix protein, namely,
tenascin in the thymus. Herein we investigated, by means of immunocytochemistry,
tenascin expression in normal infant and fetal human thymuses, as well as in cultures of
thymic microenvironmental cells.In situ, tenascin distribution is restricted to the medulla and cortico-medullary regions of
normal thymuses. This pattern thus differed from that of fibronectin, laminin and type IV
collagen, in which subseptal basement membranes were strongly labeled. Interestingly,
tenascin did not co-localize with the cytokeratin-defined thymic epithelial cell network. This
was in keeping with the in vitro data showing that tenascin-bearing cells were nonepithelial
(and probably nonfibroblastic) microenvironmental elements.Studies with fetal thymuses revealed a developmentally regulated expression of tenascin,
with a faint but consistent network labeling, in thymic rudiments as early as 12 weeks of
gestational age, that progressed to a strong TN expression at 18 weeks of fetal development,
which was similar to the distribution pattern observed thereafter, including postnatally.Our results clearly indicated that tenascin is constitutively expressed in the human
thymus, since early stages of thymic ontogeny, and suggest that the cell type responsible for
its secretion is a nonepithelial microenvironmental cell.

Claudia Sondermann Freitas

Jurandy Susana Patricia O'Campo Lyra

Sergio Ranto Dalmau

Wilson Savino

In Vivo and In Vitro Expression of Tenascin by Human
Thymic Microenvironmental Cells

Cyclosporin A (CsA), a potent inhibitor of T-cell activation, has been shown to have several
effects on thymocyte maturation, thymic stromal cells, and the generation of autoreactive T
cells. In Lewis rats, the combination of lethal irradiation, syngeneic bone marrow
transplantation, and a 4-week course of CsA administration causes the development of an
autoimmune disease (CsA-AI) resembling allogeneic graft-versus-host disease. This occurs
upon withdrawal of CsA, provided the thymus receives irradiation and is present during
CsA treatment. In this study, the separate effects of irradiation or CsA treatment on thymic
stromal cells and thymocytes, compared to the combinatory effects, were examined using
immunohistochemistry and tricolor flow cytometric analysis.CsA treatment causes an involution of the thymic medulla and a strong reduction of the
cell number of thymocytes and stromal cells residing in the medulla. However, within the
remaining medullary area, changes in cell distribution and antigen density on these cells
were not observed. Irradiation on the other hand causes a strong depletion of thymocytes.
The thymocyte population is recovered within 2 weeks and a cortical and medullary region
can be distinguished. CsA treatment in combination with irradiation results in a strongly
inhibited recovery of the medulla during CsA treatment, whereas the cortex recovers to
normal size and morphology. The presence of the medullary IDC and epithelial cells is
reduced proportionally to the small size of the medulla. However, the distribution of these
stromal cells is normal. During the CsA administration, the thymuses from irradiated and
CsA-treated rats are very similar to thymuses from CsA-treated rats. In conclusion, no
changes specific for irradiation plus CsA treatment have been observed. Regarding the
distribution and size of medullary stromal cells and residing thymocytes, thymuses from
irradiated and CsA-treated rats hardly differ from the thymuses from rats treated only with
CsA. Therefore, irradiation seems essential in the generation of CsA-AI by eliminating
suppressor-cell circuits in the periphery.

Leo J.J. Beijleveld

Jan G.M.C. Damoiseaux

Peter J.C. Van Breda Vriesman

Differential Effects of X-Irradiation and Cyclosporin-A
Administration on the Thymus with Respect to the
Generation of Cyclosporin-A-Induced Autoimmunity

Cyclosporin A (CsA) inhibits the development of mature thymocytes from their
CD4+ CD8+ precursors, but may allow autoreactive cells to mature. Using 3-color flow
cytometry, we have followed the progressive development of thymocytes, including
potentially autoreactive cells, during CsA treatment. Numbers of CD4+ CD8+ CD3high
thymocytes dropped immediately, suggesting that the generation of these mature thymocyte
precursors, normally dependent upon positive selection, was inhibited by CsA.
Numbers of CD4- CD8+ thymocytes also declined rapidly, but CD4- CD8+ thymocytes
were unaffected lfor 2 days, suggesting that the mature single-positive subsets are not
symmetrically derived from a common GsA-sensitive precursor. An exceptional subset of
CD8 SP thymocytes, expressing CD45RA, did not respond to CsA for about 10 days,
indicating that they are distantly derived from a CsA-sensitive precursor. Apoptosis of
TCR-Vβ3+ thymocytes caused by Mtυ-6, quantified according to the down-regulation of
CD4 and CD8 on immature thymocytes, was partially inhibited by CsA, to maximal effect
within 24 hours. This did not, however, facilitate their development into mature thymocytes.

Russell D.J. Huby

Ray Hicks

Lindsey K. Goff

Kinetics of Thymocyte Subset Development and Selection
Revealed by Cyclosporin A Treatment

Sublethal irradiation of the murine thymus has been a useful tool for depleting the thymus
of dividing immature thymocyte subsets, to sequence thymocyte differentiation events
occurring from radiation-resistant precursors. This massive reduction in thymocytes also
represents a model in which the bidirectional interplay between the thymic stromal cells
and lymphocytes can be investigated. The purpose of this study was thus twofold: to
precisely map the initiation of thymopoiesis as a prelude to assessing the effects of injected
mAb to novel thymic antigens; and to use a panel of mAbs to determine the alterations in
the thymic stroma during the T-cell depletion and reconstitution phases. The striking
finding from this study was that following T-cell depletion, there was a marked upregulation
of specific stromal antigens, which retracted with the reappearance of T cells. Thus,
following sublethal irradiation, there are modifications in the thymic microenvironment that
may be necessary to support renewed thymopoiesis and the complete restoration of the
thymus involved the synchronous development of both the stromal and lymphocytic
components.

Elise S. Randle-Barrett

Richard L. Boyd

Thymic Microenvironment and Lymphoid Responses to
Sublethal Irradiation

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Journal of Immunology Research - Table of contents 1995

title

Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

Journal of Immunology Research

Table of Contents

Table of Contents: 1995

γ/δ Cells in Fetal, Neonatal, and Adult Rat Lymphoid Organs

Interleukin Gene Expression in Mouse Preimplantation Development

Hemopoiesis in the Thymus

A Common Stem Cell for Murine Cortical and Medullary Thymic Epithelial Cells?

In Vivo and In Vitro Expression of Tenascin by Human Thymic Microenvironmental Cells

Differential Effects of X-Irradiation and Cyclosporin-A Administration on the Thymus with Respect to the Generation of Cyclosporin-A-Induced Autoimmunity

Kinetics of Thymocyte Subset Development and Selection Revealed by Cyclosporin A Treatment

Thymic Microenvironment and Lymphoid Responses to Sublethal Irradiation