Early pregnancy factor suppresses the infiltration of lymphocytes and macrophages in the spinal cord of rats during experimental autoimmune encephalomyelitis but has no effect on apoptosis.
Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties that has been shown to suppress acute experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP) in Lewis rats. EAE is associated with infiltration of the central nervous system (CNS) with inflammatory cells. Spontaneous recovery involves the loss of T lymphocytes from the CNS and the selective apoptosis of Vbeta8.2+ cells. In the present study, T cell, macrophage (CD11b/c+) and B cell (CD45RA+) populations in spinal cord and popliteal lymph nodes (LN) of Lewis rats with EAE were quantitated and apoptosis was studied. Rats were treated with EPF or vehicle. Following treatment on day 14 after inoculation with MBP, neither 1 x 100 microg nor 2 x 100 microg doses of EPF affected the total number of cells infiltrating the spinal cord on day 15, although the higher dose caused a decrease in the number of CD5+ and CD11b/c+ cells. Treatment with 2 x 100 microg/day from days 10 to 14 decreased the total number of infiltrating cells, and the numbers of CD5+, CD11b/c+ and CD45RA+ cells. Apoptosis was unaffected. No alteration on the number or type of inflammatory cells in the popliteal LN was observed after treatment on days 10-14. However, treatment with EPF from days 0 to 11 increased the total number of T and B cells and CD5+ T cells found on day 12 in the LN. Similarly, there was an increase in the frequency of MBP-reactive cells in the LN as determined by limiting dilution analysis. These results suggest that EPF treatment reduces the numbers of lymphocytes and macrophages in the CNS, possibly through an effect on cell trafficking.
Athanasas-Platsis
Stavrosia
S
Department of Medicine, The University of Queensland, Royal Brisbane Hospital, Queensland 4029, Australia. epf.group@mailbox.uq.edu.au
Zhang
Bing
B
Hillyard
Narelle C
NC
Cavanagh
Alice C
AC
Csurhes
Peter A
PA
Morton
Halle
H
McCombe
Pamela A
PA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D018835:Chaperonin 10; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004676:Myelin Basic Protein; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011257:Pregnancy Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D011930:Reaction Time / Q000187:drug effects / Q000276:immunology; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D013491:Suppressor Factors, Immunologic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D018835:Chaperonin 10; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D010455:Peptides; D011257:Pregnancy Proteins; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor