Dynamics and requirements of T cell clonal expansion in vivo at the single-cell level: Effector function is linked to proliferative capacity

Citation
H. Gudmundsdottir et al., Dynamics and requirements of T cell clonal expansion in vivo at the single-cell level: Effector function is linked to proliferative capacity, J IMMUNOL, 162(9), 1999, pp. 5212-5223
Citations number
39
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
162
Issue
9
Year of publication
1999
Pages
5212 - 5223
Database
ISI
SICI code
0022-1767(19990501)162:9<5212:DAROTC>2.0.ZU;2-Z
Abstract
The adoptive transfer of TCR-transgenic T cells into syngeneic recipients a llows characterization of individual T cells during in vivo immune response s. However, the proliferative behavior of individual T cells and its relati onship to effector and memory function has been difficult to define, Here, we used a fluorescent dye to dissect and quantify T cell proliferative dyna mics in vivo, We find that the average Ag-specific CD4(+) T cell that under goes division in vivo generates >20 daughter cells. TCR and CD28 signals co operatively determine the degree of primary clonal expansion by increasing both the proportion of Ag-specific T cells that di ride and the number of r ounds of division the responding T cells undergo. Nonetheless, despite opti mal signaling, up to one-third of Ag-specific cells fail to divide even tho ugh they show phenotypic evidence of Ag encounter. Surprisingly, however! t ransgenic T cells maturing on a RAG-2(-/-) background exhibit a responder f requency of 95-98% in vivo! suggesting that maximal proliferative potential requires either a naive phenotype or allelic exclusion at the TCR alpha lo cus. Finally, studies reveal division cycle-dependent expression of markers of T cell differentiation, such as CD44, CD45RB, and CD62L and show also t hat expression of the cytokines IFN-gamma and IL-2 depends primarily on cel l division rather than on receipt of costimulatory signals, These results p rovide a quantitative assessment of T cell proliferation in vivo and define the relationship between cell division and other parameters of the immune response including cytokine production, the availability of costimulation, and the capacity for memory.