Stimulation of Human Lymphocytes by Allogenic Macrophages in vitro

Abstract

Macrophages were obtained from human peripheral blood by incubating mononuclear cells in plastic tissue culture flasks. After 1—14 days, the cells were used in mixed lymphocyte macrophage cultures. Macrophages could not, themselves, be stimulated to proliferation by allogenic cells, but stimulated allogenic lymphocytes. By the use of responding cells and stimulating macrophages from HLA‐D homozygous individuals, the HLA‐D determinants could be shown to be responsible for the stimulation of allogenic lymphocytes.

Stimulation of T Lymphocytes by Autologous non‐T Lymphoid Cells. Participation of HLA‐D?

“…However, the stimulation of T cells by autologous adherent cells alone was not significantly above background. In allogeneic mixed lymphocyte cultures, macrophages are shown to exert a significant stimulation, but in our case, the stimulation was weaker than that of the corresponding B cells (Kaakinen et al 1977). Whether auto-stimulation is also caused by the Ig-negative Fc receptorpositive "K" cell, as suggested by experiments of Kuntz et al (1976), cannot be ruled out by our investigations, since…”

Different Stimulating Capacity of Monocytes and B Lymphocytes in Mixed Leukocyte Cultures: A Dose Response Study

“…1976, Oehler & Herberman 1977. This could explain why the two authors who used mononuclear cells instead of purified lymphocytes as responders, as we did in this study, have found that large amounts of dlogeneic monocytes had inhibiting effects on MLC (Albrechtsen & Lied 1978, Kaakinen & Hirschberg 1977. In such cases the number of monocytes among responders would add up t o that of stimulators and rapidly provide an excess of these cells.…”

“…The sharper slope of the regression line obtained with B stimulators indicates that they induce a stronger expansion of the clone of responding cells than other preparations in response to increasing numbers of stimulators. Differences in s:imulation kinetics by B cells as compared to the other cells are probably not implicated since they have been reported to be essentially similar with all cell fractions studied (Albrech tsen & Lied 1978, Kaakinen & Hirschberg 1977. It could be that initially stimulated antigen-specific cells, as well as secondarily recruited non-specific cells, are measured or that HLA-D antigens are more immunogenic on B cells than on monocytes.…”

“…Both B celIs and macrophages express HLA-D determinants (Hirschberg et al 1976, Kaakinen & Hirschberg 1977 which are known to induce the strongest response in MLC. However, our findings indicate that monocytes are more potent stimulators than B lymphocytes, the difference being most pronounced a t the lower numbers of cells.…”

“…Indeed, HLA-DR antigens (Human la-like) are expressed on monocytes, albeit in apparently low amounts (Drew et al 1978) and HLA-D determinants are present on macrophages (Hirschberg e t al. 1976, Kaakinen & Hirschberg 1977. However, there have been conflicting reports regarding the activating capacity of these cells, which has been reported to be stronger (Rode & Gordon 1974) or, on the contrary, weaker (Van Oers & Zeijlemaker 1977, Kaakinen & Hirschberg 1977, Albrechtsen & Lied 1978, than that of lymphocytes.…”