Document Type

Thesis

Date of Degree

Summer 2011

Degree Name

MS (Master of Science)

Degree In

Pathology

First Advisor

Vladimir P. Badovinac

Abstract

The extent to which the progeny of one primary memory CD8 T cell differs from the progeny of one naïve CD8 T cell of the same specificity remains an important question. In order to explore cell autonomous functional differences between naïve and memory CD8 T cells that are not influenced by differences in the priming environment, an experimental model has been developed in which physiological numbers of both populations of cells were co-transferred into naïve host before antigen-stimulation. Interestingly, naïve CD8 T cells expand in numbers more than primary memory CD8 T cells after various infections or immunizations. The intrinsic ability of one naïve CD8 T cell to give rise to more effector CD8 T cells than one memory CD8 T cell is independent of the number of primary memory CD8 T cells present in vivo. The sustained proliferation of primary, but not the increased death of secondary effectors was shown to contribute to the differences in the observed magnitudes of expansion. In addition, longitudinal analysis of primary and secondary CD8 T cell responses revealed that the ability of naïve CD8 T cells to generate long-lived progeny (`memory generation potential') is better than for primary memory CD8 T cells despite the differences in overall kinetics of both responses after infection. Taken together, the data presented here revealed previously unappreciated differences between naïve and memory CD8 T cells and will help further define the functional potential for both cell types.

The goal of immunization is to generate memory CD8 T cells of sufficient quality and quantity, and it has been shown that the naïve to primary memory CD8 T cell differentiation in vivo is controlled, at least in part, by the amount and duration of inflammation present early after the initiation of the response. In experiments where naïve CD8 T cells were co-transferred with increasing numbers of primary memory CD8 T cells, we observed a negative correlation between the number of primary memory present and the magnitude of primary CD8 T cell responses. Interestingly, the conversion of newly recruited (either TCR-Tg or endogenous) primary CD8 T cells into CD8 T cells with the phenotype (CD62Lhi, CD27hi) and function (tissue distribution, Ag-driven proliferation, cytokine production) of long-term memory was facilitated when they were primed in the presence of memory CD8 T cells of the same or unrelated specificity. Therefore, these data suggest that the presence of anti-vectorial immunity will not necessarily decrease the efficacy of CD8 T cell vaccination since newly recruited CD8 T cells, despite their decreased magnitude of expansion, might differentiate into functional memory cells faster.

Keywords

anti-vectorial immunity, immunity, Memory CD8 T cells, Naive CD8 T cells

Pages

vii, 94 pages

Bibliography

Includes bibliographical references (pages 88-94).

Copyright

Copyright 2011 Matthew David Martin

Included in

Pathology Commons

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