Regulatory activity of the human CD8+ cell subset: a comparison of CD8+ cells from the intestinal lamina propria and blood.

Abstract

This study was done to better define the immunoregulatory mechanisms in the human intestinal lamina propria (LP). Peripheral blood (PB) and LP cells were obtained from patients having intestinal resections. CD4+ and CD8+ cell subsets were isolated using hybridoma antibodies in a panning technique. Graded numbers of LP and PB CD8+ cells were added to cultures of autologous fresh B cells plus CD4+ cells plus pokeweed mitogen. After 10 days incubation in vitro, the supernatants were collected, and IgM and IgA synthesis was measured by isotype-specific sandwich ELISA. Both PB and LP CD8+ cells suppressed IgM and IgA synthesis by indicator cultures consisting of 5 X 10(4) B cells plus 5 X 10(4) CD4+ cells to a comparable extent. However, when these same CD8+ cells were added to indicator cultures of 5 X 10(4) B cells plus 10(5) CD4+ cells, PB CD8+ cells still suppressed, but LP CD8+ cells enhanced IgM and IgA synthesis. LP but not PB CD8+ cells also augmented IgM and IgA synthesis in cultures with suboptimal immunoglobulin synthesis. Despite these results, LP CD8+ cells were not able to provide help for B cell immunoglobulin synthesis when these two cell types were cultured together with pokeweed mitogen. The mechanism of immunoglobulin augmentation by LP CD8+ cells appeared to involve antagonism of a CD4+ rather than CD8+ suppressor cells. We conclude that functional heterogeneity is more evident within the LP CD8+ subset, with both suppressor and contra-suppressor activities demonstrable, with the latter representing a major activity in LP but not in PB CD8+ cells.