title: Induction of acute graft-versus-host disease by T cells that do not respond to in vitro alloantigen stimulation.
abstract: The mixed lymphocyte reaction (MLR) has been used extensively to measure alloreactive T cells. In clinical practice, a negative MLR of recipient T cells responding to donor cells does not necessarily mean that a donor-specific tolerance has been established. This discrepancy indicates that the presently used methods fail to demonstrate the full repertoire of alloreactive T cells. This could be the result of the fact that some alloreactive T cells do not respond in vitro but will mount a response towards alloantigens in vivo, or that some alloreactive T cells do not respond during the MLR but will respond later if the alloantigen stimulation remains. We therefore examined the non-proliferating T-cell population in a mouse primary alloreactive response. Spleen and lymph node cells derived from C57BL/6J (H-2(b)) mice were stained with carboxy-fluorescein diacetate succinimidyl ester and injected intravenously into C.B-17 severe combined immunodeficient (SCID) mice (H-2(d)). The donor cells were recovered 5 d after the injection. The non-proliferating T cells were sorted and were non-reactive to alloantigen stimulation in vitro. Nevertheless, these non-proliferating T cells could proliferate and cause acute graft-versus-host disease after being adoptively transferred to secondary recipients of SCID mice. These results suggest that there exists an alloreactive T-cell population that does not respond to in vitro alloantigen stimulation but can mount a delayed alloresponse in vivo.
authors.affiliation: Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore.
authors.forename: Jen Yan
authors.initials: JY
authors.lastname: New
authors.forename: Soh Ha
authors.initials: SH
authors.lastname: Chan
authors.forename: Eu Hian
authors.initials: EH
authors.lastname: Yap
authors.forename: Huaizhong
authors.initials: H
authors.lastname: Hu
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D002455:Cell Division / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D007519:Isoantigens