Thymosin alpha1 accelerates restoration of T cell-mediated neutralizing antibody response in immunocompromised hosts.
Thymosin alpha1 is a biological response modifier that has been used clinically for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracellular mechanisms have been postulated to explain the effect of thymosin alpha1 on hepatocytes infected with hepatitis B virus (HBV). Here, we established a new animal model and the related suitable conditions to access the thymosin activity by means of measuring the production of neutralizing antibody against hepatitis B surface antigen (HBsAg). We proved that chemically synthesized thymosin alpha1 restored the T cell-mediated antibody production following its suppression in mice by 5-fluorouracil (5-FU), and found that thymosin alpha1 showed activity at a low dose of 30 microg/kg. Further studies utilizing the flowcytometric analysis showed that thymosin alpha1 at this dose accelerated the replenishment and maturation of thymocytes while the expression of Smoothened (Smo) of the Hedgehog (Hh)-signaling in CD4-CD8- thymocytes, the potent negative regulator of proliferative responses, was not affected. The restoration of some of the defects in the host defense systems may facilitate elimination of infectious agents, and the present study provides a novel model to define the restoration of T cell-mediated immune responses to hepatitis B virus in vivo.
Li
Chun-lin
CL
Department of Medicine, Kochi Medical School, Nankoku, Japan.
Zhang
Ting
T
Saibara
Toshiji
T
Nemoto
Yoshihisa
Y
Ono
Masafumi
M
Akisawa
Naoaki
N
Iwasaki
Shinji
S
Maeda
Takashi
T
Onishi
Saburo
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016516:CD4-CD8 Ratio; D003520:Cyclophosphamide; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil; D006510:Hepatitis B Antibodies / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced / Q000276:immunology*; D007166:Immunosuppressive Agents; D051379:Mice; D008809:Mice, Inbred C3H; D009929:Organ Size / Q000187:drug effects; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D013950:Thymus Gland / Q000187:drug effects / Q000254:growth & development
D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents; D013947:Thymosin; D003520:Cyclophosphamide; D005472:Fluorouracil; D000077596:Thymalfasin