Defective antigen presentation to a cloned T helper cell by macrophages from burned mice can be restored with interleukin-1.
T helper (Th) cell dysfunction occurring very early (i.e., 24 to 72 hours) after a 30% full-thickness burn in a murine model cannot be attributed to suppressor T cell activity. Th cell activity is influenced by the activity of antigen-presenting cells (APCs). These cells process antigen and present a complex of antigen and cell surface Ia to the T cell. Additionally, they elaborate interleukin-1 (Il-1), and these events lead to Th cell release of Il-2, expression of Il-2 receptors, and proliferation of Th cells. We examined the contribution of APCs to postburn Th cell dysfunction by using mitomycin C-treated spleen cells from normal and burned mice as an APC population. The Th cell population consisted of a cloned Th cell line (D10.G4.1) that recognizes conalbumin in the context of I-Ak and proliferates when approximately stimulated. We found that APCs from burned mice induced significantly less Th cell proliferation (p less than 0.05). This was true of unfractionated spleen cells (50.4% of control) as well as positively selected (44.2% of control) or negatively selected (51.9% of control) splenic APCs. When cocultured with APCs from control mice, APCs from burned mice did not suppress control values of Th cell proliferation. Finally, the addition of murine Il-1 in vitro to cultures of burn-derived APCs, antigen, and T cell clone restored Th cell proliferation to control levels (from 38.3% to 92.8%) without nonspecifically enhancing similar cultures employing normal APCs. Il-1 in vitro did not improve Th cell function in the absence of antigen. Thus splenic APCs from mice exhibit defective antigen presentation early after burn injury. This defect is not a result of suppressor factor production by burn APCs and can be restored by Il-1 in vitro. Th cell dysfunction early after burn injury is thus due, in part, to APC dysfunction.
Kupper
T S
TS
Green
D R
DR
Durum
S K
SK
Baker
C C
CC
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002056:Burns / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D004195:Disease Models, Animal; D007153:Immunologic Deficiency Syndromes / Q000628:therapy; D007375:Interleukin-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007375:Interleukin-1