|
Sign In to gain access to subscriptions and/or personal tools.
|
Histopathologic Approaches to Detect Changes Indicative of Immunotoxicity
C. Frieke Kuper
TNO Toxicology Division, 3700 AJ Zeist, The Netherlands
Johannes H. Harleman
Novartis Pharma AG, CH 4002 Basel, Switzerland
Hans B. Richter-Reichelm
Federal Institute for Health Protection of Consumers and Veterinary Medicine, D-14196 Berlin, Germany
Joseph G. Vos
National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands, Faculty of Veterinary Medicine, 3508 TD Utrecht, The Netherlands
Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity experiments in rodents. Regarding regulatory toxicology, histopathology of lymphoid organs and tissues is a cornerstone in the identification of immunotoxic compounds. A 2-tier testing system is usually employed in which the first tier is a general screen for (immuno)toxicity and the second tier consists of specific immune function studies, including host resistance tests or mechanistic studies. The role attributed to histopathology of lymphoid organs in the updated Organisation for Economic Cooperation and Development and Food and Drug Administration guidelines requires improvement and standardization of the histopathology procedures. Optimalization and standardization was started in an international collaborative immunotoxicity study (ICICIS). However, several problems were left unaddressed, mostly because of the few compounds tested in this study. Based on the results of the ICICIS study and the morphologic changes induced by immunotoxic/immunomodulatory compounds observed in other investigations, suggestions are given to further improve the identification and (semi)quantification of histopathologic changes in lymphoid organs and tissues.
Key Words: Lymphoid organs • thymus • spleen • lymph node • mucosa-associated lymphoid tissue (MALT) • morphology • immunosuppression • immunomodulation
References
- Arts Jhe, Kuper CF, Spoor SM, Bloksma N. (1998). Airway morphology and function of rats following dermal sensitization and respiratory challenge with low molecular weight chemicals. Toxicol Appl Pharmacol 152: 66-76.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bos J (ed) (1990). The Skin Immune System. CRC Press, Boca Raton, Florida.
- Brown AR (1992). Immunological functions of splenic B-lymphocytes. Crit Rev Immunol 11: 395-417.[Web of Science][Medline]
[Order article via Infotrieve]
- Bruder MC, Spanhaak S., Bruijntjes JP, Michielsen Cppc, Vos JG, Kuper CF (1999). Intestinal T-lymphocytes of different rat strains in immunotoxicity. Toxicol Pathol 27: 171-179.[Abstract/Free Full Text]
- Bruijntjes JP, Kuper CF, Robinson JE, Schuurman HJ (1993). Epithelium-free area in the thymic cortex of rats. Dev Immunol 3: 113-122.[Web of Science][Medline]
[Order article via Infotrieve]
- Dean JH (1997). Issues with introducing new immunotoxicology methods into the safety assessment of pharmaceuticals. Toxicology 119: 95-101.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- De Bakker JM, Kammueler ME, Muller Esm, Lam AW, Seinen W., Bloksma N. (1990). Kinetics and morphology of chemically-induced popliteal lymph node reactions in comparison with antigen-, mitogen-, and graft versus host reaction induced responses. Virchows Archiv B 58: 279-287.[Web of Science]
- De Boer NK, Kroese Fgm, Sharp JG, Perry GA (1992). Immunohistological characterization of proximal clonic lymphoid tissue in the rat. Anat Rec 233: 569-576.[CrossRef][Medline]
[Order article via Infotrieve]
- De Waal EJ, Schuurman HJ, Van Loveren H., Vos JG ( 1997). Differential effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, bis(tri-n-butyltin)oxide and cyclosporine on thymus histophysiology. CRC Cric Rev Toxicol 27: 381-430.
- Gopinath C. (1996). Pathology of toxic effects on the immune system. Inflamm Res 45(suppl 2): S74-S78.[Web of Science][Medline]
[Order article via Infotrieve]
- Greaves P. (1990). Haemopoietic and lymphatic systems. In: Histopathology of Preclinical Toxicity Studies Elsevier, Amsterdam, pp 77-115.
- Greenstein BD, Fitzpatrick Fta, Kendall MD, Wheeler MJ (1987). Regeneration of the thymus in old male rats treated with a stable analogue of LHRH. J Endocrinol 112: 345-350.[Abstract/Free Full Text]
- Hastings KL, Chang-Ho A., Alam SN, Aszalos A., Young SC, Jessop JJ, Weaver JL (1997). Points to consider for assessment of the immunotoxic potential of investigational new drugs: FDA perspective. Drug Inf J 31: 1357-1362.
- Hinton DM (1995). Immunotoxicity testing applied to direct food and colour additives: US FDA "Redbook II" guidelines. Hum Exp Toxicol 14: 143-145.[Free Full Text]
- Houben GF, Penninks AH, Seinen W., Vos JG, Van Loveren H (1993). Immunotoxic effects of the color additive caramel color. III: Immune function studies in rats. Fundam Appl Toxicol 20: 30-37.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- International Collaborative Immunotoxicity Study (ICICIS) Group Investigators (1998). Report of validation study of assessment of direct immunotoxicity in the rat. Toxicology 125: 183-210.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- International Programme for Chemical Safety (IPCS) (1996). Principles and Methods for Assessing Direct Immunotoxicity Associated with Chemical Exposure. International Programme for Chemical Safety, Environmental Health Criteria Document No 160, World Health Organization, Geneva.
- Jones JC, Ward JM, Mohr U, Hunt RD (eds) (1990). Hemopoietic System. Springer-Verlag, Berlin.
- Kanamori Y., Ishimaru K., Nanno M., Maki K., Ikuta K., Nariuchi H., Ishikawa H. (1996). Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit +IL-JR+Thy1+ lympho-hemopoietic progenitors develop. J Exp Med 184: 1449-1459.[Abstract/Free Full Text]
- Koeter Hbwm (1995). International harmonisation of immunotoxicity testing. Hum Exp Toxicol 14: 151-154.[Web of Science][Medline]
[Order article via Infotrieve]
- Kuper CF, Beems RB, Bruijntjes JP, Schuurman HJ, Vos JG ( 1992). Normal development, growth and aging of the thymus. In: Pathobiology of the Aging Rat, Vol 1, Mohr U, Dungworth DL, Capen CC (eds). ILSI Press, Washington, D.C., pp 25-49.
- Kuper CF, Koornstra PJ, Hameleers Dmh, Biewenga J., Spit BJ, Duijvestijn AM, Van Breda Vriesman Pjc, Sminia T. (1992). The role of naspharyngeal lymphoid tissue. Immunol Today 13: 219-224.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Kuper CF, Schuurman HJ, Vos JG ( 1995). Pathology in immunotoxicology. In: Methods in Immunotoxicology, Vol 1, Burleson GR, Dean JH, Munson AE (eds). Wiley-Liss, New York, pp 397-436.
- Ladicz GS, Smith C., Heaps K., Ellioo GS, Slone TW, Loveless SE (1995). Possible incorporation of an immunotoxicological functional assay for assessing humoral immunity for hazard identification purposes in rats on standard toxicology study. Toxicology 96: 225-238.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Luster MI, Munson AE, Thomas PT, Holsapple MP, Fenters JD, White KL, Lauer LD, Germolec DR, Rosenthal GJ, Dean JH ( 1988). Development of a testing battery to assess chemical-induced immunotoxicity: National Toxicology Program's guidelines for immunotoxicity evaluation in mice. Fundam Appl Toxicol 10: 2-19.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Luster MI, Portier C., Pait DG, Rosenthal GJ, Germolec DR, Corsini E., Blaylock BL, Pollock P., Kouchi Y., Craig W., White KL, Munson AE, Comment CE (1993). Risk assessment in immunotoxicology. II. Relationship between immune and host resistance tests. Fundam Appl Toxicol 21: 71-82.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Mackall CL, Punt JA, Morgan P., Farr AG, Gress RE (1998). Thymic function in young/old chimeras: Substantial thymic T cell regenerative capacity despite irreversible age-associated thymic involution. Eur J Immunol 28: 1886-1893.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Majoor GD, Wodzig WH, Vriesman Pjcvb (1991). Cyclosporininduced autoimmunity. In: Thymus Update: Thymus in Immunotoxicology, Kendall MD, Ritter MA (eds). Harwood Academic, London, pp 179-200.
- Michielsen Cppc, Bloksma N., Ultee A., Van Mil F., Vos JG (1997). Hexachlorobenzene-induced immunomodulation and skin and lung lesions: A comparison between Brown Norway, Lewis, and Wistar rats. Toxicol Appl Pharmacol 144: 12-26.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Organisation for Economic Cooperation and Development (1996). Report of the OECD Immunology Work Group Meeting, Research Triangle Park, NC, 11-12 December. Organisation for Economic Co-operation and Development, Paris.
- Richter-Reichhelm HB, Dasenbrock CA, Descotes G., Emmendörfer AC, Ernst HU, Harleman JH, Hildebrand B., Küttler K., Rühl-Fehlert CI, Schilling K., Schulte AE, Vohr HW (1995). Validation of a modified 28-day rat study to evidence effects of test compounds on the immune system. Regul Toxicol Pharmacol 22: 54-56.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Rose NR, Caturegli PP (1997). Environmental and drug-induced autoimmune diseases of humans. In: Comprehensive Toxicology, Vol 5, Lawrence DA (ed). Pergamon, Oxford, United Kingdom, pp 381-391.
- Sainte-Marie G., Bélisle C., Peng FS (1990). In: Reaction Patterns of the Lymph Node. Part I. Cell Types and Functions, Grundmann E, Vollmer E (eds). Springer-Verlag, Berlin, pp 33-63.
- Schuurman HJ, Krajnc-Franken Mam, Kuper CF, Van Loveren H, Vos JG ( 1991). Immune system. In: Handbook of Toxicologic Pathology, Haschek WM, Rousseaux CG (eds). Academic Press, San Diego, California, pp 421-487.
- Van Ewijk W (1991). T-cell differentiation is influenced by thymic micro-environments. Annu Rev Immunol 9: 591-615.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Van Loveren H, Vos JG (1989). Immunotoxicological considerations: A practical approach to immunotoxicity testing in the rat. In: Advances in Applied Toxicology, Dayan AD, Paine AJ (eds). Taylor and Francis, London, pp 143-165.
- Van Loveren H., Vos JG, De Waal EJ (1996). Testing immunotoxicity of chemicals as a guide for testing approaches for pharmaceuticals. Drug Inf J 30: 275-279.
- Vos JG (1980). Immunotoxicity assessment: Screening and function studies. Arch Toxicol Suppl 4: 95-108.[Medline]
[Order article via Infotrieve]
- Vos JG (1986). Immunotoxicity of hexachlorobenzene. In: Hexachlorobenzene, Morris CR, Cabral JRP (eds). International Agency for Research on Cancer, Lyon, France, pp 347-356.
- Vos JG, Dormans Jama, Kraal G., Krajnc EI, Krajnc-Franken Mam, Van Loveren H. (1990). Immunotoxicity of hexachlorobenzene is thymus-dependent. Toxicologist 10: 221.
- Vos JG, Krajnc EI (1983). Immunotoxicity of pesticides. In: Developments in the Science and Practice of Toxicology, Hayes AW, Schnell RC, Miya TS (eds). Elsevier, Amsterdam, pp 229-240.
- Vos JG, Kuper CF, Schuurman HJ (1997). Lymphoid tissue architecture and pathological influences of toxicants. In: Toxicology of the Immune System, Comprehensive Toxicology, Vol 5, Lawrence DA (ed). Elsevier, Oxford, United Kingdom, pp 113-129.
- Weiss L., Geduldig U. (1991). Barrier cells: Stromal regulation of hematopoiesis and blood cell release in normal and stressed murine bone marrow. Blood 78: 975-990.[Abstract/Free Full Text]
- Williams N. (1998). T cells on the mucosal frontline. Science 280: 198-200.[Free Full Text]
Toxicologic Pathology, Vol. 28, No. 3,
454-466 (2000)
DOI: 10.1177/019262330002800317
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
K. J. Randall and G. Pearse
A Dual-label Technique for the Immunohistochemical Demonstration of T-Lymphocyte Subsets in Formalin-fixed, Paraffin-Embedded Rat Lymphoid Tissue
Toxicol Pathol,
October 1, 2008;
36(6):
795 - 804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Spoor, Z. A. Radi, and R. W. Dunstan
Characterization of Age- and Gender-related Changes in the Spleen and Thymus from Control Cynomolgus Macaques Used in Toxicity Studies
Toxicol Pathol,
July 1, 2008;
36(5):
695 - 704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Burns-Naas, K. L. Hastings, G. S. Ladics, S. L. Makris, G. A. Parker, and M. P. Holsapple
What's So Special about the Developing Immune System?
International Journal of Toxicology,
March 1, 2008;
27(2):
223 - 254.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Missima and J. M. Sforcin
Green Brazilian Propolis Action on Macrophages and Lymphoid Organs of Chronically Stressed Mice
Evid. Based Complement. Altern. Med.,
March 1, 2008;
5(1):
71 - 75.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Kuper, M. Van Zijverden, C. Klaassen, M. Tegelenbosch-Schouten, and A. P.M. Wolterbeek
Effects of Cyclosporin A and Cyclophosphamide on Peyer's Patches in Rat, Exposed in utero and Neonatally or During Adult Age
Toxicol Pathol,
February 1, 2007;
35(2):
226 - 232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. R. Maronpot
Enhanced Histopathology of Lymphoid Tissues
Toxicol Pathol,
August 1, 2006;
34(5):
631 - 633.
[Full Text]
[PDF]
|
|
|
|
|
|
|
STP Immunotoxicology Working Group, P. Haley, R. Perry, D. Ennulat, S. Frame, C. Johnson, J-M Lapointe, A. Nyska, P. W. Snyder, D. Walker, et al.
STP Position Paper: Best Practice Guideline for the Routine Pathology Evaluation of the Immune System
Toxicol Pathol,
April 1, 2005;
33(3):
404 - 407.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. R. Germolec, M. Kashon, A. Nyska, C. F. Kuper, C. Portier, C. Kommineni, K. A. Johnson, and M. I. Luster
The Accuracy of Extended Histopathology to Detect Immunotoxic Chemicals
Toxicol. Sci.,
December 1, 2004;
82(2):
504 - 514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Dean
A Brief History of Immunotoxicology and a Review of the Pharmaceutical Guidelines
International Journal of Toxicology,
March 1, 2004;
23(2):
83 - 90.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. R. Germolec, A. Nyska, M. Kashon, C. F. Kuper, C. Portier, C. Kommineni, K. A. Johnson, and M. I. Luster
Extended Histopathology in Immunotoxicity Testing: Interlaboratory Validation Studies
Toxicol. Sci.,
March 1, 2004;
78(1):
107 - 115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. L. Bunn, P. J. Parsons, E. Kao, and R. R. Dietert
Exposure to Lead during Critical Windows of Embryonic Development: Differential Immunotoxic Outcome Based on Stage of Exposure and Gender
Toxicol. Sci.,
November 1, 2001;
64(1):
57 - 66.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. de Waard, J. Garssen, J. Snel, G. C. A. M. Bokken, T. Sako, J. H. J. Huis in 't Veld, and J. G. Vos
Enhanced Antigen-Specific Delayed-Type Hypersensitivity and Immunoglobulin G2b Responses after Oral Administration of Viable Lactobacillus casei YIT9029 in Wistar and Brown Norway Rats
Clin. Vaccine Immunol.,
July 1, 2001;
8(4):
762 - 767.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Tryphonas and C. Gopinath
A Synopsis of the Third International Federation of Societies of Toxicologic Pathologists Conference
Toxicol Pathol,
May 1, 2000;
28(3):
370 - 374.
[PDF]
|
|
|
|
|
