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Homeostatic proliferation of naive T cells transferred to T cell-deficient syngeneic mice is driven by low-affinity self-MHC/peptide ligands and the cytokine IL-7. In addition to homeostatic proliferation, a subset of naive T cells undergoes massive proliferation in chronically immunodeficient hosts, but not in irradiated normal hosts. Such rapid T cell proliferation occurs largely independent of homeostatic factors, because it was apparent in the absence of IL-7 and in T cell-sufficient hosts devoid of functional T cell immunity. Strikingly, immunodeficient mice raised under germfree conditions supported only slow homeostatic proliferation, but not the marked T cell proliferation observed in conventionally raised immunodeficient mice. Thus, polyclonal naive T cell expansion in T cell-deficient hosts can be driven predominantly by either self-Ags or foreign Ags depending on the host’s previous state of T cell immunocompetency.

The secretory glands of many mammals are known to produce large amounts of a gamma-A immunoglobulin (sIgA) which is shed into the external secretions. Immunofluorescent staining of the subepithelial mucosa of many types of secretory glands and tissues (e.g. mammary, lacrimal, salivary, bronchial, and nasal as well as the lamina propria along the whole of the gastrointestinal tract) has shown that the majority of all immunoglobulin-producing cells in these sites are producing IgA (1).In particular, it has been reported (2, 3) that in the rabbit approximately 80% of all immunoglobulin-producing cells in the lamina propria of the small intestine stain specifically for the alpha chain of IgA. In contrast, only 8-10% of all similar cells in the spleen and lymph nodes contain this class of immunoglobulin. The observed predominance of IgA-producing cells in the lamina propria of the intestine suggested to us the possibility that the gut of a normal animal might contain a population of precursor cells which would be capable of proliferating and giving rise to IgA-producing cells.By using a method of analysis developed by Frensdorff et al. (4,5) in which cell transfer and subsequent quantitation of immunocytes by immunofluorescence is used to assess the proliferative and differentiative potential of rabbit lymphoid cells in irradiated allogeneic hosts, we were able to show that the Peyer's patches contain an enriched source of precursors for IgA-producing cells. These cells proliferate both in the spleen and in the intestinal lamina propria and give rise to immunoglobulin-producing cells, most of which make IgA. Materials and MethodsAnlmal~.--Male rabbits, weighing between 5 and 6 lb., were obtained from B and H Rabbitry (Rockville, Md.). Approximately 96% of the rabbits we have obtained from this rabbitry were homozygous for the b4 allotypic marker, an antigenic marker on the kappa *

No abstract

Peyer’s patches are known as mucosal inductive sites for humoral and cellular immune responses in the gastrointestinal tract. In contrast, functionally equivalent structures in the respiratory tract remain elusive. It has been suggested that nasal-associated lymphoid tissue (NALT) might serve as a mucosal inductive site in the upper respiratory tract. However, typical signs of mucosal inductive sites like development of germinal center reactions after Ag stimulation and isotype switching of naive B cells to IgA production have not been directly demonstrated. Moreover, it is not known whether CTL can be generated in NALT. To address these issues, NALT was structurally and functionally analyzed using a model of intranasal infection of C3H mice with reovirus. FACS and histological analyses revealed development of germinal centers in NALT in parallel with generation and expansion of IgA+ and IgG2a+ B cells after intranasal reovirus infection. Reovirus-specific IgA was produced in both the upper respiratory and the gastrointestinal tract, whereas production of reovirus-specific IgG2a was restricted to NALT, submandibular, and mesenteric lymph nodes. Moreover, virus-specific CTL were detected in NALT. Limiting dilution analysis showed a 5- to 6-fold higher precursor CTL frequency in NALT compared with a cervical lymph node. Together these data provide direct evidence that NALT is a mucosal inductive site for humoral and cellular immune responses in the upper respiratory tract.