title: Homeostatic expansion and repertoire regeneration of donor T cells during graft versus host disease is constrained by the host environment.
abstract: Graft versus host disease (GVHD) typically results in impaired T-cell reconstitution characterized by lymphopenia and repertoire skewing. One of the major causes of inadequate T-cell reconstitution is that T-cell survival and expansion in the periphery are impaired. In this report, we have performed adoptive transfer studies to determine whether the quantitative reduction in T-cell numbers is due to an intrinsic T-cell defect or whether the environmental milieu deleteriously affects T-cell expansion. These studies demonstrate that T cells obtained from animals with graft-versus-host disease (GVHD) are capable of significant expansion and renormalization of an inverted CD4/CD8 ratio when they are removed from this environment. Moreover, these cells can generate complex T-cell repertoires early after transplantation and are functionally competent to respond to third-party alloantigens. Our data indicate that T cells from mice undergoing GVHD can respond to homeostatic signals in the periphery and are not intrinsically compromised once they are removed from the GVHD environment. We thereby conclude that the host environment and not an intrinsic T-cell defect is primarily responsible for the lack of effective T-cell expansion and diversification of complex T-cell repertoires that occurs during GVHD.
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Gorski
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Mariya
authors.initials: M
authors.lastname: Gendelman
authors.forename: Maryam
authors.initials: M
authors.lastname: Yassai
authors.forename: Ashley
authors.initials: A
authors.lastname: Krueger
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tivol
authors.forename: Brent
authors.initials: B
authors.lastname: Logan
authors.forename: Richard
authors.initials: R
authors.lastname: Komorowski
authors.forename: Sanja
authors.initials: S
authors.lastname: Vodanovic-Jankovic
authors.forename: William R
authors.initials: WR
authors.lastname: Drobyski
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D049109:Cell Proliferation; D006086:Graft vs Host Disease; D006487:Hemostasis; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D012038:Regeneration; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000637:transplantation*