Identification and characterization of the antigen-specific subpopulation of alloreactive CD4+ T cells in vitro and in vivo.
We report the identification and characterization of the small subpopulation of alloantigen-specific T cells in vitro and in vivo. This subpopulation of T cells was distinguished by up-regulation of cell surface CD4 expression. These CD4high T cells were alloantigen specific in proliferation assays in vitro, and they expressed memory/activation markers, including CD44high and CD69high. Further studies demonstrated that these allospecific CD4high cells were also present (< or = 1% of CD4+ T cells) in vivo in BALB/c (H-2d) recipients of C57BL/6 (H-2b) skin allografts. CD4high T cells isolated from regional draining lymph nodes in these skin graft recipients reacted in a donor-specific fashion to C57BL/6 splenocyte stimulator cells in mixed lymphocyte culture. Adoptive transfer of CD4high, but not CD4normal T cells, just before skin engraftment in CD4 knockout mice, reconstituted rejection. The discovery that a small subpopulation of CD4high lymph node cells contained all of the alloantigen-specific T cells may allow study of tissue-specificity and subsequent alloantigen identification in transplantation.
Krieger
N R
NR
Department of Surgery, Stanford University, CA 94305-5111, USA.
Fathman
C G
CG
Shaw
M K
MK
Ridgway
W M
WM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000276:immunology*; D000939:Epitopes; D007156:Immunologic Memory; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000737:chemistry
D000939:Epitopes; D007519:Isoantigens