The nonhuman primate as a model of developmental immunotoxicity

Andrew G Hendrickx, N. Makori, P. Peterson

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Macaques are well suited for preclinical testing of biopharmaceutics due to reproductive and developmental similarities with humans. In order to characterize ontogeny of the immune system in this model, we studied lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus macaque fetuses during the second and third trimesters [gestation days (GD) 75-145, term 165 days]. Systemic lymphoid tissues (thymus, spleen and lymph nodes, and intestinal tissue) were examined for morphology and cell surface markers by immunohistochemistry. Lymphocytes were further characterized by flow cytometry for differentiation markers. Splenic tissue from early second trimester fetuses was populated mainly by CD20+ B cells while the thymus contained large numbers of CD3+ T cells. In the late second trimester (day 80), approximately equal populations of B and T cells were present in both tissues and numerous dendritic cells (p55+) were present in the intestinal lamina propria. By the second trimester, the rhesus macaque fetal lymphoid system is well developed. Analysis of lymphoid organs from retinoic acid-treated fetuses indicated that the T-cell (thymus)-dependent compartment of the spleen white pulp in specimens with thymic aplasia showed a reduction in size and proportion of CD3+ T cells compared to controls. Our findings indicate that RA-induced thymic defects result in disrupted development of the splenic T-cell-dependent compartment.

Original languageEnglish (US)
Pages (from-to)537-542
Number of pages6
JournalHuman and Experimental Toxicology
Volume21
Issue number9-10
DOIs
StatePublished - Sep 2002

Fingerprint

T-cells
Primates
Second Pregnancy Trimester
Thymus
Tissue
T-Lymphocytes
Thymus Gland
Fetus
Lymphocytes
Lymphoid Tissue
Macaca mulatta
B-Lymphocytes
Spleen
Biopharmaceutics
Flow cytometry
Immune system
Differentiation Antigens
Third Pregnancy Trimester
Macaca
Antigen-Presenting Cells

Keywords

  • B- and T lymphocytes
  • Nonhuman primate
  • Retinoic acid
  • Safety assessment
  • Spleen
  • Thymus

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

The nonhuman primate as a model of developmental immunotoxicity. / Hendrickx, Andrew G; Makori, N.; Peterson, P.

In: Human and Experimental Toxicology, Vol. 21, No. 9-10, 09.2002, p. 537-542.

Research output: Contribution to journalArticle

Hendrickx, Andrew G ; Makori, N. ; Peterson, P. / The nonhuman primate as a model of developmental immunotoxicity. In: Human and Experimental Toxicology. 2002 ; Vol. 21, No. 9-10. pp. 537-542.
@article{c20a563a09704e8c9d7d71b1bc252523,
title = "The nonhuman primate as a model of developmental immunotoxicity",
abstract = "Macaques are well suited for preclinical testing of biopharmaceutics due to reproductive and developmental similarities with humans. In order to characterize ontogeny of the immune system in this model, we studied lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus macaque fetuses during the second and third trimesters [gestation days (GD) 75-145, term 165 days]. Systemic lymphoid tissues (thymus, spleen and lymph nodes, and intestinal tissue) were examined for morphology and cell surface markers by immunohistochemistry. Lymphocytes were further characterized by flow cytometry for differentiation markers. Splenic tissue from early second trimester fetuses was populated mainly by CD20+ B cells while the thymus contained large numbers of CD3+ T cells. In the late second trimester (day 80), approximately equal populations of B and T cells were present in both tissues and numerous dendritic cells (p55+) were present in the intestinal lamina propria. By the second trimester, the rhesus macaque fetal lymphoid system is well developed. Analysis of lymphoid organs from retinoic acid-treated fetuses indicated that the T-cell (thymus)-dependent compartment of the spleen white pulp in specimens with thymic aplasia showed a reduction in size and proportion of CD3+ T cells compared to controls. Our findings indicate that RA-induced thymic defects result in disrupted development of the splenic T-cell-dependent compartment.",
keywords = "B- and T lymphocytes, Nonhuman primate, Retinoic acid, Safety assessment, Spleen, Thymus",
author = "Hendrickx, {Andrew G} and N. Makori and P. Peterson",
year = "2002",
month = "9",
doi = "10.1191/0960327102ht294oa",
language = "English (US)",
volume = "21",
pages = "537--542",
journal = "Human and Experimental Toxicology",
issn = "0960-3271",
publisher = "SAGE Publications Inc.",
number = "9-10",

}

TY - JOUR

T1 - The nonhuman primate as a model of developmental immunotoxicity

AU - Hendrickx, Andrew G

AU - Makori, N.

AU - Peterson, P.

PY - 2002/9

Y1 - 2002/9

N2 - Macaques are well suited for preclinical testing of biopharmaceutics due to reproductive and developmental similarities with humans. In order to characterize ontogeny of the immune system in this model, we studied lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus macaque fetuses during the second and third trimesters [gestation days (GD) 75-145, term 165 days]. Systemic lymphoid tissues (thymus, spleen and lymph nodes, and intestinal tissue) were examined for morphology and cell surface markers by immunohistochemistry. Lymphocytes were further characterized by flow cytometry for differentiation markers. Splenic tissue from early second trimester fetuses was populated mainly by CD20+ B cells while the thymus contained large numbers of CD3+ T cells. In the late second trimester (day 80), approximately equal populations of B and T cells were present in both tissues and numerous dendritic cells (p55+) were present in the intestinal lamina propria. By the second trimester, the rhesus macaque fetal lymphoid system is well developed. Analysis of lymphoid organs from retinoic acid-treated fetuses indicated that the T-cell (thymus)-dependent compartment of the spleen white pulp in specimens with thymic aplasia showed a reduction in size and proportion of CD3+ T cells compared to controls. Our findings indicate that RA-induced thymic defects result in disrupted development of the splenic T-cell-dependent compartment.

AB - Macaques are well suited for preclinical testing of biopharmaceutics due to reproductive and developmental similarities with humans. In order to characterize ontogeny of the immune system in this model, we studied lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus macaque fetuses during the second and third trimesters [gestation days (GD) 75-145, term 165 days]. Systemic lymphoid tissues (thymus, spleen and lymph nodes, and intestinal tissue) were examined for morphology and cell surface markers by immunohistochemistry. Lymphocytes were further characterized by flow cytometry for differentiation markers. Splenic tissue from early second trimester fetuses was populated mainly by CD20+ B cells while the thymus contained large numbers of CD3+ T cells. In the late second trimester (day 80), approximately equal populations of B and T cells were present in both tissues and numerous dendritic cells (p55+) were present in the intestinal lamina propria. By the second trimester, the rhesus macaque fetal lymphoid system is well developed. Analysis of lymphoid organs from retinoic acid-treated fetuses indicated that the T-cell (thymus)-dependent compartment of the spleen white pulp in specimens with thymic aplasia showed a reduction in size and proportion of CD3+ T cells compared to controls. Our findings indicate that RA-induced thymic defects result in disrupted development of the splenic T-cell-dependent compartment.

KW - B- and T lymphocytes

KW - Nonhuman primate

KW - Retinoic acid

KW - Safety assessment

KW - Spleen

KW - Thymus

UR - http://www.scopus.com/inward/record.url?scp=0036759728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036759728&partnerID=8YFLogxK

U2 - 10.1191/0960327102ht294oa

DO - 10.1191/0960327102ht294oa

M3 - Article

C2 - 12458913

AN - SCOPUS:0036759728

VL - 21

SP - 537

EP - 542

JO - Human and Experimental Toxicology

JF - Human and Experimental Toxicology

SN - 0960-3271

IS - 9-10

ER -