Severe injury triggers antigen-specific T-helper cell dysfunction.
Although it is established that post-injury immune dysfunction involves alterations in T-cell function, the effects of injury on T-cell function in vivo are poorly understood. This study uses a mouse injury model and an antigen immunization approach to investigate the influence of injury on antigen-specific T-helper cell function. We report here that injury triggered a significant reduction in antigen-specific T-helper-1 (Th1)-dependent IgG2a antibody formation, while IgM, IgG1, and IgE production was unchanged. In addition, injury caused a reduction in cytokine production (IL-2, IFNgamma and IL-10) by antigen-stimulated T-cells. We also demonstrate that interleukin 12 (IL-12), a cytokine that promotes Th1 cell differentiation, restored IgG2a antibody formation and corrected the injury-induced reduction in antigen-stimulated cytokine production. Taken together, these findings indicate that severe injury induces a dramatic reduction in Th1 cell function in vivo and suggest that therapies designed to restore Th1 cell function may be beneficial to the injured host.
Kelly
J L
JL
Department of Surgery (Immunology), Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA.
O'Suilleabhain
C B
CB
Soberg
C C
CC
Mannick
J A
JA
Lederer
J A
JA
D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D002056:Burns / Q000276:immunology*; D007109:Immunity; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma