Antigen-dependent selection of T cells that are able to efficiently regulate free cytoplasmic Ca2+ levels.
In T helper cells, the process of memory acquisition is reflected in the expression of phenotypic markers. However, little is known regarding the functional changes that occurred in T helper cells selected after a primary Ag-specific response. We now present data that indicate that such T helper cells acquire the ability to down-regulate high concentrations of free cytoplasmic Ca2+. This property renders them resistant to intense inductive stimuli, such as high concentrations of ionomycin. The accumulation of cells that display this ability parallels the progressive proliferative enrichment of Ag-specific T cells and correlates with the surface expression of the CD45RB(low) isoform. As previously shown, persistent high levels of cytoplasmic Ca2+ are responsible for death via apoptosis in virgin T cells. In contrast, the ability to regulate cytosolic Ca2+ allows survival and clonal expansion. We suggest that memory T cells behave differently from virgin T cells when interacting with Ag-presenting B cells (as reported by others) because they have acquired this new physiologic property. Ag-presenting B cells deliver an intense stimulatory signal to T cells because of a high multiplicity of cognate interactions. Thus, Ag-driven T cell proliferation results in the selection of "resistant" T helper cells that can be successfully stimulated by memory B cells. In contrast, naive T cells, which cannot modulate high levels of cytosolic Ca2+, are deleted as a consequence of Ag presentation by B cells.
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
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Rajasekar
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Augustin
D000818:Animals; D000941:Antigens / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D007156:Immunologic Memory; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011978:Receptors, Nicotinic / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000941:Antigens; D011978:Receptors, Nicotinic; D015759:Ionomycin; D010047:Ovalbumin; D002118:Calcium