Dynamics of mycobacterial HSP65-induced T-cell cytokine expression during oral tolerance induction in adjuvant arthritis.
OBJECTIVE
To investigate whether oral administration of mycobacterial heat-shock protein 65 (HSP65) during adjuvant arthritis (AA) induces regulatory cells and cytokines.


METHODS
AA was induced in Lewis rats and from the time of disease onset HSP65 in the presence of soya bean trypsin inhibitor (STI) was administered orally every other day. The number of splenic CD4+CD25+ T cells and antigen-induced cytokine mRNA expression were determined.


RESULTS
Oral treatment with HSP65/STI reduced AA symptoms. After one feeding of HSP65/STI, the number of CD4+CD25+ splenic T cells increased and HSP65-specific T cells expressed increased levels of interferon gamma and interleukin 10. After two feedings, the expression of interleukin-10 mRNA remained increased, whereas there was low expression of interferon gamma mRNA. The number of CD4+CD25+ splenic T cells remained increased.


CONCLUSIONS
Oral treatment with HSP65/STI after AA onset reduces disease symptoms via dynamic changes in the number of CD4+CD25+ splenocytes and in antigen-induced cytokine production.
Cobelens
P M
PM
Department of Immunology, Wilhelmina Children's Hospital of the University Medical Center Utrecht, The Netherlands.
Kavelaars
A
A
van der Zee
R
R
van Eden
W
W
Heijnen
C J
CJ
D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins; D002478:Cells, Cultured; D018834:Chaperonin 60; D018833:Chaperonins / Q000008:administration & dosage*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008297:Male; D010940:Plant Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014361:Trypsin Inhibitors; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D010940:Plant Proteins; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D007371:Interferon-gamma; D000516:alpha-Amylases; D018833:Chaperonins