Biomedical subjects

James E Riggs

Publications and source records attributed to James E Riggs.

7 recordsLinked to original sources

PubMed2006

Age-dependent loss of naïve T cells in TCR transgenic bone marrow chimeras.

Study of immune senescence is complicated by low numbers of antigen-specific lymphocytes, particularly naïve T (Tn)cells which disappear with aging. Although T cell receptor (TCR) transgenic mice facilitate aging research, their large number of Ag-specific T cells renders their T cell pool abnormal, precluding normal in vivo immunity. To create a physiologically relevant model with measurable numbers of TCR transgenic CD4+ T cells in the context of normal lymphocytes, mixed (DO11.10+BALB/c) bone marrow (BM) chimeras were constructed. As found in normal mice, the total number of transgenic T cells and the Tn:memory T cell ratio declined with the aging of the BM chimeras. Although these shifts in T cell subsets were evident in both the lymph nodes and the spleen (SP), they were more pronounced in the SP. Unlike DO11.10 mice, transgenic T cells in the chimera acquired an effector/memory phenotype upon antigen challenge. These results reveal a pliable model to study the impact of the constriction of the Tn cell repertoire upon optimal vaccine responses in the elderly.

Adoptive Transfer↗

PubMed2004

Mls presentation by peritoneal cavity B cells.

DBA/2J spleen and peritoneal cells were compared for their ability to present the minor lymphocyte stimulatory superantigen Mls-1a. Although capable of Mls presentation in vivo, peritoneal cells were less effective than spleen cells in vitro. This difference was not due to cell concentration or culture duration. Flow cytometric comparison of spleen and peritoneal B cells revealed no significant differences in cell surface markers needed for cognate interaction with T cells. Resolution of peritoneal B cell subsets by cell sorting revealed that even though B-1 cells were capable of Mls presentation, they were less effective than B-2 cells. Mixing experiments showed that B-1 cells did not inhibit B-2 cell presentation of Mls. In contrast, total peritoneal cells inhibited T cell responses to Mls presented by spleen cells. The peritoneal cavity harbors B cells that can present Mls as well as other cells that can suppress this response.

Animals↗

PubMed2004

Differential effects of CD28 costimulation upon cytokine production by CD4+ and CD8+ T cells.

The impact of CD28 ligation upon CD4+ and CD8+ T lymphocyte proliferation and cytokine production was assessed. Although costimulation increased the proliferative response of both T cell subsets, cytokine production was most markedly increased in the CD4+ subset, as evidenced by a 40-fold increase in interleukin-2 (IL-2), a 14-fold increase in interleukin-3 (IL-3) and 5-fold increases in interferon gamma and GM-colony-stimulating factor (CSF) production. The CD8+ T cell response to CD28 ligation was less marked, maxima being a 5-fold increase in IL-2 production and 2-fold increases in IL-3 and GM-CSF production. Resolution of CD4+ and CD8+ T cells into their CD44lo (naïve) and CD44hi (memory/effector) subsets revealed that naive CD4+ T cells were the most CD28-responsive subsets. CD28-mediated costimulation promotes distinct differentiation programs in CD4+ versus CD8+ T cells.

Animals↗

PubMed2004

Nonlymphoid peritoneal cells suppress the T cell response to Mls.

Comparative analyses of the ability of lymphoid tissue to present the minor lymphocyte stimulatory (Mls) superantigen Mls-1a in vitro revealed that all tissues containing mature B cells, except peritoneal cavity (PerC) cells, induced Mls-1a-specific T cell activation. Irradiation and mitomycin C treatment, addition of IL-2 and IL-12, and neutralization of IL-10 and TGF-beta did not restore Mls-1a antigen presentation by PerC cells. Co-culture studies revealed that PerC cells actively suppress the T cell response to Mls-1a. PerC cells from severe-combined immune-defective (SCID) mice also suppressed this response indicating that nonlymphoid cells mediate this effect. These results suggest that in addition to antigen processing and presentation, resident peritoneal cavity cells may temper lymphocyte activation.

Animals↗

PubMed2003

Impact of aging upon DBA/2J B cells.

The influence of age on B lymphocyte phenotype and function in DBA/2J mice was examined. The B cells of this strain express the endogenous minor lymphocyte stimulatory (Mls) retroviral superantigen (SAg) Mls-1a permitting assessment of age-related changes in cognate B cell-T cell interaction. Relative to young DBA/2J mice (< 8 months), old mice (> 17 months) had greater numbers of B cells expressing high levels of IgM and low levels of the CD11b and CD5 antigens characteristic of B-1 B cells. As measured by the T cell proliferative response to Mls, the B cells from old DBA/2J mice had reduced ability to present SAg. Upon interaction with Mls-activated T cells, old B cells secreted more IgM while young B cells made more IgG1, IgG3, and IgG2a. DBA/2J BCL functioned poorly as Mls APCs and made considerably less serum Ig. T cells from old mice exhibited a lower response to SAg and were less capable of promoting B cell differentiation. These results indicate that aging influences the cellular collaboration necessary for humoral immunity.

Aging↗

PubMed2002

Age-related changes in mature CD4+ T cells: cell cycle analysis.

T cell proliferative responses decrease with age, but the mechanisms responsible are unknown. We examined the impact of age on memory and naive CD4(+) T cell entry and progression through the cell cycle using acridine orange to identify cell cycle stage. For both subsets, fewer stimulated cells from old donors were able to enter and progress through the first cell cycle, with an increased number of cells arrested in G(0) and fewer cells in post G(0) phases. The number of dead cells as assessed by sub-G(0) DNA was also significantly greater in the old group. CD4(+) T cells from old mice also exhibited a significant reduction in clonal history as assessed by CFSE staining. This was associated with a significant decline in cyclin D2 mRNA and protein. We propose that decreases in cyclin D2 are at least partially responsible for the proliferative decline found in aged CD4(+) T cells.

Acridine Orange↗

PubMed2002

Age-dependent increase of peritoneal B-1b B cells in SCID mice.

The impact of increasing age upon immunoglobulin production and B-lymphocyte generation in "leaky" severe combined immune-defective (SCID) mice was examined by enzyme-linked immunosorbent assay and flow cytometry. By 1 year of age, the mice had normal numbers of B cells in their peritoneal cavity, while their spleen had very few immunoglobulin M-positive (IgM+) cells. The majority of B cells expressed the CD11b marker characteristic of the B-1b subset. B-1a (CD5+) cells were present at a lower frequency and B-2 cells were absent. The frequency of mice producing detectable immunoglobulin increased with age, and isotype diversity within individual mice was variable. IgM production was most frequently observed followed by IgG3 and IgG2a, then IgG1, and finally IgA. The selective persistence of the B-1 B-cell subset in the peritoneal cavity of aging SCID mice is a natural model for the study of those genetic and environmental influences that determine lymphocyte longevity.

Aging↗