Synergy Among Lymphoid Cells Mediating the Graft-Versus-Host Response

Abstract

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 106 for the young and 10 x 106 for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 106 young cells and 4 x 106 old cells) produced reactions approximately equal to those obtained with 5 x 106 young cells. As few as 0.25 x 106 young cells were sufficient to effect a reaction when combined with 4.75 x 106 old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.

Synergy Among Responding Lymphoid Cells in the One-Way Mixed Lymphocyte Reaction

“…Our experiment using combinations of thymocytes and LN cells in which either one of the populations consisted of F1 hybrid cells derived from mice of the B6-responding strain and the CBA-stimulating strain indicated that in the MLR model (8), just as in the GVH model (1), both responding populations must be allogeneic to the stimulating cells to participate in synergy. Also, synergy was not observed if either responding cell population was inactivated, via freezing and thawing by Cantor et al (14), or in our experiments by pretreatment with mitomycin-C.…”

“…While in the GVH reaction a clear relationship exists between the response as measured in the Simonsen assay and the logarithms of the cell doses in the range 0.5-20 X 10 ~ cells/mouse (14), we observed in the range of 1-8 X 106 cells/ml in MLR a more or less linear relationship between [aH]thymidine uptake and numbers of responding cells. Above a certain cell concentration (about 12 × 106 cells/ml), no further increase could be obtained under the conditions of our test.…”

“…The effects of antithymocyte serum on the MLR and upon synergy were assessed. While minor differences exist and are herein described, our overall results strongly suggest that in our experiments with synergy in MLR, we may be dealing with the same T1-and T2-cell subpopulations described by Cantor and Asofsky and coworkers (1,2,4,5,14) as displaying synergy in the graft-vs.-host reaction.…”

Regulatory Mechanisms in Cell-Mediated Immune Responses

“…The spleen is comprised of functionally heterogeneous populations of lymphocytes; subpopulations of T cells of varying stages of maturity and function are represented (1)(2)(3)(22)(23)(24). Spleen or spleen-seeking cells are less reactive in MLR than lymph node or lymph node-seeking cells (23).…”

Alteration of lymphocyte function in nzb/nzw mice

“…Graft-versus-host reactions were measured by a modified Simonsen assay as described previously (16,17).…”