Age-related persistent clonal expansions of CD28(-) cells: phenotypic and molecular TCR analysis reveals both CD4(+) and CD4(+)CD8(+) cells with identical CDR3 sequences.
In a small group of subjects we had identified persistent expansions (range 6-72%) of CD4(+)CD8(+) double-positive (DP) peripheral blood (PB) cells which express the CD8 alpha/alpha homodimer. Here, DP cells present in a larger cohort were further investigated and found by FACS analysis to express a single or a dominant TCRBV family. In these subjects, with a mean age of about 64 years, expansions of CD4(+) cells with the same TCRBV family specificity as in the respective DP cells also were consistently detected. TCR heterogeneity of the dominant TCRBV family was specifically evaluated: The amplified CDR3 region was cloned and found to consist of one single or two largely dominant sequence patterns. Furthermore, cloning of the CDR3 region from FACS-sorted DP, CD4(+), or CD8(+) cells indicates that both DP and CD4(+), but not CD8(+) cells, isolated from the same individual possess a striking identity of the CDR3 regions. As indicated by FACS analysis, the clonally expanded cells occur in the CD4(+)CD28(-) cells. Taken together, these results suggest that expanded CD4(+)CD28(-) cells might also acquire CD8 alpha/alpha expression and become DP and imply that CD4 clonality is a more frequent phenomenon than previously suspected. In conclusion, the persistent expansions described in this report represent a novel group of age-related benign clonal expansions of still undefined significance of a rare CD28(-) T cell subset.
Divisione di Oncologia Sperimentale 2, Centro di Riferimento Oncologico di Aviano, Italy.
A
A
Colombatti
R
R
Doliana
M
M
Schiappacassi
C
C
Argentini
E
E
Tonutti
C
C
Feruglio
P
P
Sala
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D018106:CD28 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D002999:Clone Cells / Q000166:cytology* / Q000276:immunology*; D022801:Complementarity Determining Regions; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D006801:Humans; D007137:Immunoglobulin alpha-Chains / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism
D018106:CD28 Antigens; D022801:Complementarity Determining Regions; D007137:Immunoglobulin alpha-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta