Regulatory role of host CD8+ T lymphocytes in experimental graft-versus-host disease across a single major histocompatibility complex class II incompatibility.
BACKGROUND
CD8+ T cells are known to regulate type 2 helper T cell (Th2) alloreactive immune responses but their mode of activation is unclear. We investigated the role of host CD8+ T cells in experimental Th2-type graft-versus-host disease (GVHD) where donor/recipient disparity is restricted to a single major histocompatibility complex (MHC) class II antigen.


METHODS
Immunoglobulin (Ig) E serum levels, eosinophilia and lymphoid tissue hyperplasia were compared after injection of bm12 CD4+ T cells in either wild-type or CD8+ T cell-deficient (CD8-/-) C57BL/6 mice. In vitro, we explored effects of the addition of CD8+ T cells from wild-type or IFN-gamma-/- mice in mixed leukocyte cultures prepared with beta2 microglobulin-deficient (beta2m-/-) CD4+ T cells as responders or beta2m dendritic cells as stimulators.


RESULTS
HyperIgE resolved after 3 weeks in wild-type hosts whereas it persisted for 6 weeks in CD8-/- hosts. Eosinophil infiltrates in lymph nodes were significantly enhanced in CD8-/- hosts. Increased serum levels of IL-5 and IL-13 in CD8-/- hosts confirmed the enhancement of Th2-type responses in the context of recipient CD8+ T cell deficiency. Hyperplasia of lymph nodes and spleen were similar in both groups, as well as in vivo proliferation of donor CD4+ T cells. In vitro, CD8+ T cell regulation of the alloreactive Th2 response depended on their production of IFN-gamma and did not require expression of beta2m on CD4+ T cells or antigen-presenting cells.


CONCLUSIONS
Host CD8+ T cells regulate alloreactive Th2 responses during graft-versus-host disease through an IFN-gamma dependent pathway, independently of the recognition of beta2m-associated MHC class I molecules.
de Lavareille
Aurore
A
Institute for Medical Immunology, Université Libre de Bruxelles, and Department of Pathology, Erasme Hospital, Brussels, Belgium.
Prigogine
Cynthia
C
Paulart
Frédéric
F
Nagy
Nathalie
N
Habran
Claude
C
Haddou
Najate Ouled
NO
Le Moine
Alain
A
Salmon
Isabelle
I
Goldman
Michel
M
Flamand
Véronique
V
D000818:Animals; D001787:Blood Group Incompatibility / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D004802:Eosinophilia / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000097:blood*; D007073:Immunoglobulin E / Q000096:biosynthesis; D018793:Interleukin-13 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D007518:Isoantibodies / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency
D000949:Histocompatibility Antigens Class II; D018793:Interleukin-13; D015848:Interleukin-5; D007518:Isoantibodies; D001613:beta 2-Microglobulin; D007073:Immunoglobulin E