Burn injury primes naive CD4+ T cells for an augmented T-helper 1 response.
BACKGROUND
The mechanisms responsible for altered T-cell responses and cytokine production after injury are not well understood. We used T-cell receptor (TCR) transgenic mice to study burn injury effects on naive versus antigen-activated CD4+ T cells in vivo.


METHODS
One week after sham or burn injury, lymph node cells were prepared from TCR transgenic mice and stimulated with TCR transgene-specific antigens. T-cell proliferation was measured and culture supernatants were tested for interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, and IL-10 by enzyme-linked immunosorbent assay (ELISA). Burn injury effects on antigen-activated T cells were studied by immunizing TCR transgenic or wild-type mice at the time of injury.


RESULTS
The antigen-stimulated proliferation of native CD4+ T cells was unaffected by burn injury and no increase in T-helper 2 (Th2)-type cytokine production was observed. Instead, burn injury augmented INF-gamma production by naive CD4+ transgenic T cells, and IL-2 production was marginally reduced. Thus, burn injury primed native T cells for an enhanced Th1-type response. In contrast, antigen-specific proliferation, IL-2, and IFN-gamma production by T cells harvested from immunized wild-type mice were suppressed. Unexpectedly, high mortality was observed when burn-injured TCR transgenic mice were immunized.


CONCLUSIONS
Our results show that burn injury has differential effects on naive and antigen-activated CD4+ T cells and can prime naive CD4+ T cells.
Kavanagh
E G
EG
Department of Surgery (Immunology), Harvard Medical School/Brigham and Women's Hospital, Boston, Mass 02115, USA.
Kelly
J L
JL
Lyons
A
A
Soberg
C C
CC
Mannick
J A
JA
Lederer
J A
JA
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002056:Burns / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000096:biosynthesis
D000941:Antigens; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin