Lymphopenia-Induced Homeostatic Proliferation of CD8 super(+) T Cells Is a Mechanism for Effective Allogeneic Skin Graft Rejection following Burn Injury

• Published in: Journal of Immunology Vol. 176; no. 11; pp. 6717 - 6726
• Main Authors: Maile, Robert, Barnes, Carie M, Nielsen, Alma I, Meyer, Anthony A, Frelinger, Jeffrey A, Cairns, Bruce A
• Format: Journal Article
• Language: English
• Published: 01.06.2006
• ISSN: 0022-1767; 1365-2567

Burn patients are immunocompromised yet paradoxically are able to effectively reject allogeneic skin grafts. Failure to close a massive burn wound leads to sepsis and multiple system organ failure. Immune suppression early (3 days) after burn injury is associated with glucocorticoid-mediated T cell apoptosis and anti-inflammatory cytokine responses. Using a mouse model of burn injury, we show CD8 super(+) T cell hyperresponsiveness late (14 days) after burn injury. This is associated with a CD8 super(+) T cell pro- and anti-inflammatory cytokine secretion profile, peripheral lymphopenia, and accumulation of a rapidly cycling, hyperresponsive memory-like CD8 super(+)CD44 super(+) IL-7R super(-) T cells which do not require costimulation for effective Ag response. Adoptive transfer of allospecific CD8 super(+) T cells purified 14 days postburn results in enhanced allogeneic skin graft rejection in unburned recipient mice. Chemical blockade of glucocorticoid-induced lymphocyte apoptosis early after burn injury abolishes both the late homeostatic accumulation of CD8 super(+) memory-like T cells and the associated enhanced proinflammatory CD8 super(+) T cell response, but not the late enhanced CD8 super(+) anti-inflammatory response. These data suggest a mechanism for the dynamic CD8 super(+) T cell response following injury involving an interaction between activation, apoptosis, and cellular regeneration with broad clinical implications for allogeneic skin grafting and sepsis.