TH1/TH2 cytokine profile of the immune response in limb component transplantation.
BACKGROUND
The purpose of this study was to define the cytokine secretion pattern during limb allograft rejection and to determine its correlation to differential tissue antigenicity of limb allograft components.


METHODS
Twenty-five C57Bl/6 mice (H-2Kb) were randomized to six groups. The experimental groups were recipients of vascularized Balb/c mice (H-2Kd) allografts consisting of skin, muscle, whole limb, or limb with the skin removed or nonvascularized nerve allografts. The unmodified rejection response was studied by histology, flow cytometry, and ELISPOT assay to quantify IFN-gamma (Th1) and IL-4 (Th2) production.


RESULTS
The greatest Th1 response was seen in the recipients of allografts composed of skin (973.3 +/- 93 spots/million spleen cells; mean +/- SEM), followed by whole limb (961.3 +/- 86/million), nerve (613.3 +/- 245/million), limb with skin removed (483 +/- 246/million), and then muscle (460 +/- 234/million). Recipients of skin, whole limb, and nerve allografts had the highest IFN-gamma:IL-4 ratios, or greatest Th1 deviation, of 3.1 +/- 0.4, 3.0 +/- 0.2, and 2.9 +/- 0.6, respectively. These were significantly greater than those that received muscle (0.9 +/- 0.3) and limb allografts with skin removed (1.0 +/- 0.4) (p < 0.05).


CONCLUSIONS
The skin component produced the greatest Th1 activation of the immune response and appears to be a critical component of the overall antigenicity of the whole limb allograft, as evidenced by the Th2 shift seen when the skin was removed. Muscle produced the least Th1 differentiation, with nerve being intermediate.
Tung
Thomas H
TH
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA. tungt@msnotes.wustl.ed
Mohanakumar
T
T
Mackinnon
Susan E
SE
D000818:Animals; D005121:Extremities / Q000637:transplantation*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000276:immunology / Q000637:transplantation; D011897:Random Allocation; D016038:Skin Transplantation / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014184:Transplantation, Homologous