Soluble HLA class I molecules induce apoptosis in alloreactive cytotoxic T lymphocytes

Abstract

Soluble HLA class I molecules (sHLAs) have been identified in the serum of patients with inflammatory diseases, allografts and autoimmune diseases and in serum of healthy individuals. The biological significance of these molecules, particularly after allogeneic organ transplantation, has been enigmatic. Here we show that primary alloreactive CD8+ T cells interact with sHLA and undergo apoptosis in the absence of a second signal. Ligation of CD28 rescued T cells from death, implying that sHLAs induce apoptosis through selective stimulation of the T-cell receptor. CD95-L was upregulated after cytotoxic T lymphocytes were incubated with sHLAs, and cell death was blocked by a neutralizing anti-CD95-L antibody, suggesting that sHLAs induce endogenous mutual killing of activated T cells. These results provide a molecular basis for the capacity of sHLAs to downregulate T-cell responses, which may be especially relevant to organ transplantation.

Soluble HLA-G: Are they clinically relevant?

“…Like classical sHLA class I antigens (27,28), sHLA-G have been shown by Fournel et al (29) and by one of us (30) to induce apoptosis of activated CD8 + T cells and CD8 + NK cells, although this result has not been confirmed by Hunt (31) who however used recombinant HLA-G in her experiments. Binding to CD8 leads to Fas ligand (L) upregulation, soluble FasL secretion and activated CD8 + cell apoptosis by Fas/sFasL interaction [30].…”

Apoptosis in liver transplantation: A mechanism contributing to immune modulation, preservation injury, neoplasia, and viral disease

“…An alternative mechanism for induction of immune privilege may involve soluble HLA class 1 moleculeinduced CTL apoptosis. 33 …”

Elevated serum HLA class I levels coincide with acute and chronic graft-versus-host disease

“…[15][16][17][18] In kidney transplant significantly. Kinetic studies gave no evidence that the recipients, however, this correlation is still controversial.…”

“…Results 0.94 g/ml and 18.73 g/ml (mean 4.81 ± 4.30 g/ml). The pre-BMT sHLA-I levels of 12 patients receiving autosHLA-I class I levels in healthy individuals and in BMT logous BMT ranged between 1.64 g/ml and 17.33 g/ml recipients before BMT (mean 6.59 ± 5.36 g/ml) and the pre-BMT levels of 34 Normal sHLA-I levels were determined in a total of 36 allogeneic BMT patients ranged between 0.28 g/ml and healthy blood and bone marrow donors and ranged between 16.85 g/ml (mean 4.07 ± 3.50 g/ml). The differences in sHLA-I levels of healthy blood and bone marrow donors 4.5 g/ml of the pre-BMT level with the exception of ⌬sHLA-I of two patients (UPNs 45 and 54) whose sHLAand autologous or allogeneic BMT patients pre-BMT were not significant (data not shown).…”

“…No during rejection episodes. [13][14][15][16][17][18] The liver is a major source changes in sHLA-I levels (⌬sHLA-I) occurred in autoof sHLA-I as has been shown in liver transplant recipients, logous and allogeneic BMT patients without GVHD. In where up to 50% of the total sHLA-I found in the recipient contrast, sHLA-I reached high levels in patients sufferafter transplantation is of donor-type.…”