Role of in situ IL-2r and TGF-beta expression in tolerant vascularized bone marrow (limb) transplant chimeras.
We hypothesized that an increase in IL-2 activated T cells in situ within the marrow component of a transplanted limb may adversely affect development of tolerance, while increased TGF-beta expression locally would facilitate tolerance induction and/or maintenance. Digital image analysis of cellular expression of IL-2r in the bone marrow was significantly increased in the CON and TXP limbs for both GVHD and tolerant recipients as compared to normal limb marrow (P < .02). The amount of cellular expression of TGF-beta was significantly increased in the GVHD animals, both CON and TXP, as compared to the tolerant animals (43.2 +/- 3.1 vs 10.6 +/- 2.6; P < .000001). Our results show that increased IL-2r and TGF-beta expression in situ within the bone marrow is an important effect common to both alloimmune tolerance and GVHD induction with VBMT chimeras. The dramatic increase in the expression of TGF-beta in the GVHD transplanted limbs may explain the profound immunosuppression that results. Additionally, moderate expression of TGF-beta in situ in tolerant chimeras may represent a mechanism for the induction and maintenance of tolerance.
Tatem
L D
LD
Department of Surgery, Robert Wood Johnson Medical School, Cooper Health System, USA.
Hirpara
S
S
Dalsey
R M
RM
Iannacone
W M
WM
DeLong
W G
WG
Hewitt
C W
CW
D000818:Animals; D001853:Bone Marrow / Q000098:blood supply; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016025:Bone Transplantation / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006614:Hindlimb / Q000637:transplantation*; D007108:Immune Tolerance; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D018183:Transplantation Chimera / Q000276:immunology*
D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta