T Cell Activation Pathways: B7, LFA-3, and ICAM-1 Shape Unique T Cell Profiles.

Two signals are required for induction of cell proliferation and cytokine production in resting T cells. Occupancy of the T cell receptor by antigen/MHC complexes delivers the first signal to the T cell, while the second signal is provided by interaction with costimulatory ligands on APC. CD2, LFA-1, and CD28 are the major costimulatory and adhesive molecules on T cells and bind to the LFA-3, ICAM-1 and B7 ligands, respectively, on APC. LFA-3 plays a central role for naive and memory T helper cells during the early phase of an immune response. The LFA-3/CD2 pathway initiates strong antigen-independent cell adhesion, substantial expansion of naive T helper cells, and induction of large amounts of IFN-γ in memory cells. The release of IFN-γ may upregulate expression of ICAM-1 and B7 on APC and allows multiple adhesion pathways to amplify the immune response. The LFA- 1/ICAM-l pathway stimulates adhesion and cell proliferation more efficiently in memory T helper cells than in naive cells. Further, the results suggest that naive T helper cells express functionally inactive LFA-1 molecules on the cell surface, which may have a physiological role in keeping these cells in a resting state. B7 costimulation superinduces IL-2 production in both naive and memory T helper cells and generates long-lasting cell proliferation. This permits transition from an autocrine to a paracrine immune response. Coexpression of B7/LFA-3 provides an optimal APC function and enables a vigorous T cell response to minute amounts of antigen. AP-1 and NF-κB transcription factors are involved in the induction of several cytokine gene promoters and play a central role in the regulation of IL-2 gene transcription. LFA-3 costimulation only moderately enhances AP-1 DNA-binding activity and does not influence the NF-κB activity induced by TCR engagement, whereas B7 costimulation induces large amounts of NF-κB and AP-1 activity in T helper cells. The costimulatory ligands represent a family of adhesion molecules with considerable redundancy. Interfamily redundancy of LFA-3, B7, and ICAM ligands offers an opportunity to regulate distinct T cell response profiles in various microenvironments at separate time points of an immune response.

A STUDY ON THE ESTRADIOL-INDUCED AUGMENTATION OF A SPECIFIC CELL PRODUCT IN THE VAGINAL EPITHELIUM OF THE NEONATAL MOUSE.

The epithelial content of an estradiol-sensitive immunological marker (CVA) has been quantified by mixed haemagglutination on tissue sections from the vagina of neonatal mice exposed to different schedules of estradiol treatment. Daily administration of estradiol-17ß (5 µg/day) was especially efficient in elevating the CVA content when the hormone was administered during the first four days after birth. Following a single injection of estradiol-17ß (5 µg in aqueous suspension) on one of the first five days of life, the vaginal epithelium reacted with a more vigourous CVA accumulation when challenged with estradiol at a later time. The effect was most pronounced for days 2 and 3. The possibility that this early effect of estradiol may involve other mechanisms than those operative in the estradiol action at later stages, is discussed.