Dark Agouti (DA) rats are highly susceptible to induction of Th-l-mediated autoimmunity
disease, including experimental allergic encephalomyelitis (EAE). In contrast to other susceptible
rat strains in which disease is induced only with encephalitogen emulsified in complete
Freund's adjuvants (CFA), in DA rats EAE develops after injection of encephalitogen in
incomplete Freund's adjuvants (IFA) or Titermax, putative Th-2 directed adjuvant. Lymph
node cells derived from immunized DA rats and stimulated invitro produce significantly
more Interferon-<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mtext>γ</mml:mtext></mml:math> (IFN-<mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mtext>γ</mml:mtext></mml:math>) than resistant Albino Oxford (AO) rats. However, cells derived
from both strains produce large amounts of IL-10 but not IL-4. Immunized lymph node cells
derived from EAE susceptible (AO × DA) F1rats induce clinical signs of disease in sublethally
irradiated parental DA but not AO rats. The pathohistology of the target tissue in these
recipients clearly demonstrated infiltration of mononuclear cells in both parental strains.
However, the number of CD4+ cells was significantly higher and number of apoptotic cells
significantly lower in DA rats sacrificed 8 days after passive transfer. We postulate that in
addition to higher IFN-<mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mtext>γ</mml:mtext></mml:math> and TNF-α production, resistance to early apoptosis of the invading
cells in the target tissue possibly due to lack of downregulation by TGF-β leads to exceptional
susceptibility to EAE in DA rats.

Miodrag L. Lukic

Eric Mensah-Brown

Sehamuddin Galadari

Allen Shahin

Lack of Apoptosis of Infiltrating Cells as the Mechanism
of High Susceptibility to EAE in DA Rats

Incidence of apoptosis was investigated in the spleen and lymph nodes of +/+, CD18 -/- and
urokinase receptor (uPAR, CD87) -/- mice, untreated or Plasmodium Berghei Anka (PbA)
infected. In non infected mice, incidence of apoptosis was lower in the lymph nodes of CD18
-/- and uPAR -/- than in +/+ mice, as seen by FACS analysis to count the number of hypodiploid
and Annexin-V binding cells. Infection of mice with PbA resulted in a marked increase
in the size of spleen and lymph nodes 7–8 days after infection, which was slightly higher in
uPAR -/- and CD18 -/- than in +/+ mice. PbA infection increased about 7 fold the incidence of
apoptosis in the lymphoid organs of +/+, especially in the white pulp and germinal centers of
the spleen and lymph nodes, while in contrast it was unchanged in PbA infected CD18 -/- or
uPAR -/- mice. Serum IgG levels, and number of circulating leukocytes were significantly
higher in both uPAR and CD18 -/- than in +/+ mice. These results indicate that the CD18 and
uPAR surface molecules, which are known to be associated in the cell membrane, have an
important influence upon the incidence of cell survival in both normal or stimulated lymphoid
organs.

Pierre Francois Piguet

Chen da Laperrousaz

Christian Vesin

Yves Donati

Incidence of Apoptosis in the Lymphoid Organs of Normal
or Malaria Infected Mice is Decreased in CD18 and
Urokinase - Receptor (UPAR, CD87) Deficient Mice

X-linked agammaglobulinemia (XLA) is one of the most frequent inherited immunodeficiency
diseases in man and is characterized by an almost complete arrest of B cell differentiation
at the pre-B cell stage. The gene defective in XLA encodes the cytoplasmic signaling
molecule Bruton's tyrosine kinase (Btk). Next to the CBA/N strain of mice, carrying a single
amino acid substitution mutation in the Btk gene, which results in the X-linked immunodeficiency
(xid) phenotype, additional mouse models have been developed to study the role of
Btk invivo. This review discusses the analyses of Btk null-mutants, obtained by gene targeting
in embryonic stem cells, and transgenic mice that express wild-type or mutated forms of
the Btk gene. These studies provided information on the function of Btk at several important
checkpoints throughout B cell development. Analyses of the mouse models indicated that Btk
is not essential for pre-B cell receptor signaling in the mouse. By contrast, Btk-mediated B
cell receptor signaling appears to be required for the survival of immature B cells in the bone
marrow, that have performed a successful immunoglobulin (Ig) L chain locus rearrangement,
resultirig in the expression of a non-autoreactive Ig on the membrane. Btk is also shown to be
involved in signaling pathways that govern the development of peripheral B cells, including
follicular entry, follicular maturation and plasma cell differentiation.

Alex Maas

Rudolf W. Hendriks

Role of Bruton's Tyrosine Kinase in B Cell Development

PP are first visible at <mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>∼</mml:mo></mml:math>15.5 wk gestation after which there is a rapid spurt in the development
and maturation of lymphoid follicles so that at any given point of time new foci of PP development
are continuously formed at a rapid rate. Addition of rows of follicles results in the
formation of a PP. Immature PP of younger fetuses have a spongy structure in contrast with
the compact lymphoid follicles of mature PP of older fetuses. Immunocytochemical studies
reveal that there is a subtle gradation in the expression of lymphocyte surface markers with
increasing fetal age. Expression of antigenic markers occurs in an ordered sequence viz. HLA – DR, CD19 (B cell population), CD9 (pre-B cells), CD3 T lymphocytes, CD4 helper / inducer lymphocytes, the CD8 suppressor / cytotoxic cells and lastly, the CD57 Natural Killer cells. The antigens are expressed first on lymphocytes of PP and thereafter in those of the appendix. Our findings clearly demonstrate that the <mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>∼</mml:mo></mml:math>5 wk fetal period from 17.5 wk to 22 wk
represents a major growth phase in the development of surface markers of lymphocytes in the
mucosal immune system of the gut.

S. A. Bhide

K. V. Wadekar

S. A. Koushik

Peyer's Patches Are Precocious to the Appendix in Human Development

The number, phenotype, localisation and development of intraepithelial lymphocytes (IEL)
from duodenum (Du) and ileum (Il) were studied by immunohistochemistry (IHC) and light
and electron microscopy in unweaned (0–7 weeks old) and six months-old pigs. Developmental
changes at birth showed that 38% of the total lymphocytes in the villi were IEL, mainly of
the CD2+CD4-CD8- double negative (DN) phenotype. That proportion rose to over 50% at
week 5 after birth, resembling adult proportion, although still with fewer cells than in adult
pigs. CD4+ cells appeared relatively early in life although they were confined to the lamina
propria (LP) and CD8+ cells were found only in low numbers. In the villi of adult animals,
almost half of the total number of lymphocytes were IEL (49% Du, 52% Il). Over half of
these IEL (52% Du, 53% Il) showed the CD2+CD4-CD8+ phenotype and were localized at
the epithelium's basement membrane. Numerous (43% Du, 42% Il) DN IEL were found
grouped at the enterocyte nucleus level and relatively few (5% in Du and Il) granular IEL
were found apically in the epithelium. These proportions were homogeneously maintained
along the villi's tip, middle and bottom, suggesting that the IEL may have their origin in the
LP. Therefore, the IEL compartment in the porcine intestine develops slowly with age and is
actually composed by a heterogeneous population of cells (null, DN and CD8+). These
results may explain the increased susceptibility of young animals to disease during the lactation
period and should be taken into account when functional studies are carried out with IEL.
The quantitative results of this paper established a model for studies on the effect of age, diet,
normal flora, infection and oral immunization on the IEL of the gut.

M.  A. Vega-López

G. Arenas-Contreras

M. Bailey

S. González-Pozos

C. R. Stokes

M. G. Ortega

R. Mondragón-Flores

Development of lntraepithelial Cells
in the Porcine Small Intestine

The production of dendritic cells (DC) from haemopoietic progenitors maintained in long
term stroma-dependent cultures (LTC) of spleen or bone marrow (BM) occurs independently
of added granulocyte/macrophage colony stimulating factor (GM-CSF). The possibility that
cultures depend on endogenous GM-CSF produced in low levels was tested by attempting to
generate LTC from spleen and BM of GM-CSF-/- mice. Multiple cultures from GM-CSF-/-
and wild type mice were established and compared for cell production. GM-CSF-/- LTC
developed more slowly, but by 16 weeks produced cells resembling DC in numbers comparable
to wild type cultures. LTC maintained distinct populations of small and large cells, the latter
resembling DC. Cells collected from GM-CSF-/- LTC were capable antigen presenting
cells (APC) for T cell stimulation and morphologically resembled DC. Large cells expressed
the CD11b, CD11c, CD86, 33D1 and Dec-205 markers of DC. Addition of GM-CSF to
GM-CSF-/- LTC increased the proportion of large, mature DC present in culture. Stromal cells
from GM-CSF-/- LTC could support the differentiation of DC from early progenitors maintained
in LTC without addition of GM-CSF. However, GM-CSF is not a critical factor in the invitro generation of DC from progenitors. It can, however, substitute for stromal cells in
increasing the survival of mature DC.

Keping Ni

Helen C. O'Neill

Development of Dendritic Cells from GM-CSF-/-
Mice invitro: GM-CSF Enhances Production
and Survival of Cells

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

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Journal of Immunology Research - Table of contents 2001

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