Effects of murine leukemia viruses on the function of dendritic cells.
In asymptomatic human immunodeficiency virus-1 infection T cells respond normally to allogeneic dendritic cells (DC), but DC show reduced stimulatory capacity. By contrast in HTLV-1 infection no significant changes in allogeneic stimulation were seen but DC-stimulated activity of autologous T cells. In seeking animal models relevant to these diseases the effects of two murine leukemia retroviruses, Rauscher leukemia virus (RLV) and Moloney leukemia virus (MLV) on the function of dendritic cells and T cells in a primary mixed leucocyte reaction have been tested. Treatment by RLV in vitro suppressed the ability of DC to stimulate allogeneic T cells from healthy animals. MLV at the same concentration did not significantly affect the ability of DC to stimulate allogeneic T cells, but provoked considerable enhancement of the low level stimulation by DC in the syngeneic system. Similar results were obtained following in vivo exposure to viruses. Two pieces of evidence suggested that these effects were due to impairment of DC function and were not operating through infection of T cells. Firstly, exposure of T cells directly to virus in vitro and in vivo before stimulation with untreated allogeneic DC caused no significant alteration in T cell activity. Secondly, the impact of murine leukemia virus on DC function was not abrogated when infected DC were added to normal T cells and cultured in the presence of zidovudine. Treatment of DC by RLV caused a decrease of cluster formation with allogeneic T cells. No statistically significant influence of MLV was observed on cluster formation after 3-h of incubation in the allogeneic system. However, after 18-h incubation MLV-treated DC formed fewer clusters with T cells than untreated DC. At the same time a stimulatory effect of MLV on DC cluster formation with syngeneic T cells was found. Considerable decrease was found in major histocompatibility complex class II antigen and LFA-1 receptor expression on the DC surface in mice infected by RLV. MLV induced no significant changes. These mouse retroviruses can therefore cause changes in DC function similar to those already reported using human retroviruses and may provide models for studying their effects.
Gabrilovich
D I
DI
Antigen Presentation Group, Clinical Research Centre, Harrow, GB.
Roberts
M S
MS
Harvey
J J
JJ
Botcherby
M
M
Bedford
P A
PA
Knight
S C
SC
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006649:Histocompatibility Antigens / Q000378:metabolism; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000276:immunology*; D011925:Rauscher Virus / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology
D006649:Histocompatibility Antigens; D016169:Lymphocyte Function-Associated Antigen-1