Heterogeneity of the circulating human CD4+ T cell population. Further evidence that the CD4+CD45RA-CD27- T cell subset contains specialized primed T cells.

Baars, Paul A.; Maurice, M. M.; Rep, M.H.G.; Hooibrink, Berend; Lier, R. A. W. Van

doi:10.4049/jimmunol.154.1.17

Cited by 100 publications

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“…In these cases, the MF elevations are thought to be due to increased T-cell proliferation (Abramson et al, 1999), which can be both mutagenic and serve to amplify pre-existing T-cell mutants. For this reason, the HPRT mutation assay also can be used as a reporter for environmental immunotoxicity to detect heightened immunological activity by employing, in principle, mutation as a surrogate marker for cell division (Baars et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Clonality, trafficking, and molecular alterations among Hprt mutant T lymphocytes isolated from control mice versus mice treated with N‐ethyl‐N‐nitrosourea

Judice,

Sussman,

Walker

et al. 2023

Environ and Mol Mutagen

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Mutations in T lymphocytes (T‐cells) are informative quantitative markers for environmental mutagen exposures, but risk extrapolations from rodent models to humans also require an understanding of how T‐cell development and proliferation kinetics impact mutagenic outcomes. Rodent studies have shown that patterns in chemical‐induced mutations in the hypoxanthine‐guanine phosphoribosyltransferase (Hprt) gene of T‐cells differ between lymphoid organs. The current work was performed to obtain knowledge of the relationships between maturation events during T‐cell development and changes in chemical‐induced mutant frequencies over time in differing immune compartments of a mouse model. A novel reverse transcriptase‐polymerase chain reaction based method was developed to determine the specific T‐cell receptor beta (Tcrb) gene mRNA expressed in mouse T‐cell isolates, enabling sequence analysis of the PCR product that then identifies the specific hypervariable CDR3 junctional region of the expressed Tcrb gene for individual isolates. Characterization of spontaneous Hprt mutant isolates from the thymus, spleen, and lymph nodes of control mice for their Tcrb gene expression found evidence of in vivo clonal amplifications of Hprt mutants and their trafficking between tissues in the same animal. Concurrent analyses of Hprt mutations and Tcrb gene rearrangements in different lymphoid tissues of control versus N‐ethyl‐N‐nitrosourea‐exposed mice permitted elucidation of the localization and timing of mutational events in T‐cells, establishing that mutagenesis occurs primarily in the pre‐rearrangement replicative period in pre‐thymic/thymic populations. These findings demonstrate that chemical‐induced mutagenic burden is determined by the combination of mutagenesis and T‐cell clonal expansion, processes with roles in immune function and in the pathogenesis of autoimmune disease and cancer.

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Section: Introductionmentioning

confidence: 99%

Clonality, trafficking, and molecular alterations among Hprt mutant T lymphocytes isolated from control mice versus mice treated with N‐ethyl‐N‐nitrosourea

Judice,

Sussman,

Walker

et al. 2023

Environ and Mol Mutagen

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Intestinal lymphangiectasia, a disease characterized by selective loss of naive CD45RA+ lymphocytes into the gastrointestinal tract

Fuss¹,

Strober²,

Cuccherini³

et al. 1998

Eur. J. Immunol.

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Intestinal lymphangiectasia (InL) is a disease characterized by hypoproteinemia and lymphocytopenia resulting from blocked intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract. This leads to immunologic abnormalities including hypogammaglobulinemia, skin anergy and impaired allograft rejection. In the present study, we evaluated whether the above immunologic abnormalities are secondary to a quantitative or qualitative disorder of T cells. In initial studies we demonstrated that adult InL patients' peripheral blood contain strikingly (and significantly) reduced numbers of CD4+/CD45RA+ T cells, whereas the numbers of CD4+/CD45RO+ T cells were only moderately (and not significantly) reduced. In addition, the CD4+/CD45RO+ T cell population contained an increased percentage of highly differentiated and previously sensitized cells, as demonstrated by decreased CD27 and CD31 expression and increased HLA-DR and CD69 expression. In subsequent functional studies, we showed that the InL CD4+/CD45RO+ T cells, when stimulated in vitro, proliferate fivefold less than control CD4+/CD45RO+ T cells and produce fourfold more IL-4 and threefold less IFN-gamma and IL-2. Thus, this cytokine production profile also reflects the highly differentiated nature of the residual cell population. Overall, these studies provide new information on the trafficking of naive/mature and Th1/Th2 T cell populations in this disease model.

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Distribution of human CMV-specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoforms

et al. 1999

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Chronic antigenic stimulation has been associated with peripheral blood expansions of CD8pos. T cells characterized by CD57 expression, loss of CD27 expression, and reversal of the CD45RObright /RAdim phenotype usually associated with immunological memory towards a CD45ROdim /RAbright phenotype. However, the relationship and functional significance of these subset(s) has remained controversial. Here, this issue was addressed using a novel flow cytometric technique that allows simultaneous detection of human cytomegalovirus (HCMV)‐specific CD8pos. memory T cells by rapid (< 6 h) HCMV peptide‐specific induction of cytokine synthesis, and their phenotypic characterization, including CD57, CD27 and CD45RA/RO. The vast majority of resting CD8pos. T cells capable of rapid induction of IFN‐γ and TNF‐α synthesis in response to HCMV peptides were found in a subset characterized by intermediate to high expression of CD57, down‐regulation/loss of CD27, and varying degrees of reversal of the classical “memory” CD45RObright /RAdim phenotype. This subpopulation likely includes the fully differentiated memory cells responsible for the long‐term immune defense against HCMV reactivation.

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Heterogeneity of the circulating human CD4+ T cell population. Further evidence that the CD4+CD45RA-CD27- T cell subset contains specialized primed T cells.

Cited by 100 publications

References 0 publications

Clonality, trafficking, and molecular alterations among Hprt mutant T lymphocytes isolated from control mice versus mice treated with N‐ethyl‐N‐nitrosourea

Clonality, trafficking, and molecular alterations among Hprt mutant T lymphocytes isolated from control mice versus mice treated with N‐ethyl‐N‐nitrosourea

Intestinal lymphangiectasia, a disease characterized by selective loss of naive CD45RA+ lymphocytes into the gastrointestinal tract

Distribution of human CMV-specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoforms

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