Thymic hormone modulation of age-induced changes in the induction of graft-versus-host disease by DBA/2J lymphocytes.
Aging induces a number of changes in the immune system, including the involution of the thymus which results in the loss of thymic hormone production and alteration in T cell function. One age-dependent change in immune response is the increasing risk of developing acute or chronic form of graft-versus-host disease (GVHD) following bone marrow transplantation as the age of the recipient increases. A murine model of GVHD that has been extensively studied is one in which injection of C57BL/6 spleen cells into unirradiated B6D2F1 mice results in an acute form of GVHD characterized by cytolytic T lymphocytes (CTL), suppressor cells, runting, and occasionally death. In contrast, injection of DBA/2J spleen cells results in a chronic form of GVHD characterized by a lack of CTL and hyperproduction of immunoglobulin and autoantibodies. This study shows that the GVHD response of DBA/2J spleen cells is dependent on the age of the donor DBA/2J mice. If spleen cells from DBA/2J mice older than 3 months are injected into B6D2F1 recipients, CTL and lack of immunoglobulin production indicative of acute GVHD result. Administration of thymosin fraction 5, a collection of thymic hormones, to DBA/2J mice older than 3 months caused spleen cells from these treated mice to give a GVHD response characteristic of the chronic form of GVHD in B6D2F1 recipients. Thus, thymic hormones were able to modulate the changes in GVHD responses of DBA/2 lymphocytes that occur as the mice age. Preliminary fractionation of TF5 has indicated that there are at least two active thymic peptides present in TF5.
Fast
L D
LD
Department of Medicine, Rhode Island Hospital, Providence.
Kouttab
N M
NM
Badamchian
M
M
Goldstein
A L
AL
D000375:Aging / Q000276:immunology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006086:Graft vs Host Disease / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology
D010455:Peptides; C033782:thymosin fraction 5; D013947:Thymosin