Detection of CD40 on human thyroid follicular cells: analysis of expression and function.
Thyroid follicular cells (TFC) are a common target of autoimmune attack, but the role they play in inciting and maintaining this attack is unclear. TFC express cytokines, adhesion molecules, and class I and II major histocompatibility complex molecules, but without additional signals that costimulate T cells, they may down-regulate, rather than stimulate, T cell function. In this report, we have investigated whether TFC can express the CD40 molecule, which plays a crucial role in the reciprocal two-way communication between T and B cells. We have shown by immunohistochemistry and flow cytometry that CD40 is expressed by TFC in vivo and in vitro in both autoimmune and nonautoimmune glands. CD40 expression was up-regulated by interleukin-1alpha and interferon-gamma, but not by TSH. Although there was no significant effect of CD40 ligation on cAMP synthesis or [3H]thymidine incorporation, there was a significant increase in interleukin-6 release by TFC. Thus, although TFC do not express members of the B7 family of T cell costimulators, they do express CD40, indicating the possibility of mutually stimulatory T cell-TFC interaction. This has important implications, both for TFC synthesis of immunological mediators and for the biasing of T cell behavior toward a T helper 2-type phenotype.
Metcalfe
R A
RA
Department of Medicine, University of Sheffield, Clinical Sciences Center, Northern General Hospital, United Kingdom.
McIntosh
R S
RS
Marelli-Berg
F
F
Lombardi
G
G
Lechler
R
R
Weetman
A P
AP
D013956:Antithyroid Agents / Q000494:pharmacology*; D019013:CD40 Antigens / Q000032:analysis*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D011869:Radioligand Assay; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013972:Thyrotropin / Q000494:pharmacology*
D013956:Antithyroid Agents; D019013:CD40 Antigens; D016207:Cytokines; D015850:Interleukin-6; D013972:Thyrotropin; D000242:Cyclic AMP; D013936:Thymidine