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From the Departments of Microbiology and Pathology, Yale University School of Medicine, New Haven, Connecticut 06510
Abstract
We immunized chimeric mice, which had chromosomally marked (T6) T cells, with sheep red cells (SRBC) or saline and then gave them injections of 3H-thymidine every 6 hr for 4, 8, or 12 days. At intervals thereafter, we reimmunized them with SRBC, horse RBC (HRBC), KLH, or saline, and did autoradiographic and karyotypic studies of their spleen cells. We identified a population of T cells which synthesize DNA within the first 4 days after immunization and then remain relatively quiescent until a further immunization, at which time they divide again. No B cell population behaves similarly, even when the period of labeling is extended to 12 days. The T cell response is highly specific in that HRBC immunization fails to activate cells labeled after SRBC immunization. A major portion of the T cells dividing in the secondary response are unlabeled. Control studies indicate that most of these unlabeled cells did not divide in the primary response nor were they naive T cells making a simple concomitant primary response. We conclude that some long-term memory T cells are generated by antigen-induced division of precursor cells. The cellular basis for T cell memory, however, cannot be ascribed entirely to the proliferation of a clone of cells. Either memory cells are generated by nonproliferative mechanisms and/or T memory cells recruit other T cells to respond.
Footnotes
1 This work was supported by National Institutes of Health Grants AI-10,497 and AI-06545 from the National Institute of Allergy and Infectious Disease and Grant CA-08593 from the National Cancer Institute.
2 Richard K. Gershon is a recipient of a Career Development Award (CA 10,316) from the National Cancer Institute.
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