The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear phagocytes in the body, yet little is known about the cellular mechanisms that regulate mononuclear cell recruitment to noninflamed and inflamed intestinal mucosa. Here, we show that intestinal macrophages do not proliferate. We also show that a substantial proportion of intestinal macrophages express chemokine receptors for interleukin (IL)-8 and transforming growth factor-beta (TGF-beta), and a smaller proportion expresses receptors for N-formylmethionyl-leucyl-phenylalanine and C5a, but, surprisingly, they do not migrate to the corresponding ligands. In contrast, autologous blood monocytes, which express the same receptors, do migrate to the ligands. Blood monocytes also migrate to conditioned medium (CM) derived from lamina propria extracellular matrix, which we show contains IL-8 and TGF-beta that are produced by epithelial cells and lamina propria mast cells. This migration is specific to IL-8 and TGF-beta, as preincubation of the stroma-CM with antibodies to IL-8 and TGF-beta significantly blocked monocyte chemotaxis to the stromal products. Together, these findings indicate that blood monocytes are the exclusive source of macrophages in the intestinal mucosa and underscore the central role of newly recruited blood monocytes in maintaining the macrophage population in noninflamed mucosa and in serving as the exclusive source of macrophages in inflamed mucosa.

T-T hybridomas, produced by fusions between R1.1 T lymphoma and cloned T helper cells that promote IgA responses (Th A cells) were characterized in this study. A total of 85 cloned cell lines were produced, and their supernatants were assessed for support of antigen-dependent IgA (and IgM and IgG) responses. 16 of 85 culture fractions supported IgA anti-sheep red blood cell, -horse red blood cell, or -trinitrophenyl responses in either lipopolysaccharide-triggered splenic B cell, or normal Peyer's patch B cell cultures, and the responses were specific for the antigen used for in vitro immunization. None of the supernatants from the cell lines induced significant polyclonal responses in these B cell cultures. Interestingly, the 16 hybridomas that produced supernatants with IgA-promoting properties had Fc receptors for IgA (Fc alpha R), but did not express Fc mu R or Fc gamma R. When supernatants from Fc alpha R+ T cell lines were subjected to IgA affinity chromatography, the IgA-promoting activity bound to IgA (IBF alpha) and was recovered in the eluate. No binding of active fractions occurred when supernates were passed through IgM or IgG immunoadsorbent columns. High concentrations of purified IBF alpha suppressed T-dependent IgA responses, while an optimal level was required for enhancement of this isotype response. These results suggest that Fc alpha R+ hybridomas derived from Th A cells release IBF alpha into the culture medium, and that these molecules regulate IgA responses to various T-dependent antigens.