Karen Roessner

High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis

γδ T cells accumulate at epithelial barriers and at sites of inflammation in various infectious and autoimmune diseases, yet little is understood about the function of tissue-infiltrating γδ T cells. We observe that γδ T cells of the Vδ1 subset accumulate in synovial fluid of human Lyme arthritis and are intensely cytolytic toward a wide array of target cells. Particularly striking is that the cytolytic activity is highly prolonged, lasting for at least 3 wk after stimulation of the γδ T cells with Borrelia burgdorferi. Cytolysis is largely Fas dependent and results from very high and prolonged expression of surface Fas ligand, which is transcriptionally regulated. This also manifests in a substantial level of self-induced apoptosis of the γδ T cells. In this capacity, certain γδ T cell subsets may serve as cytolytic sentinels at sites of inflammation, and perhaps at epithelial barriers.

Lyme Arthritis Synovial γδ T Cells Instruct Dendritic Cells via Fas Ligand

γδ T cells participate in the innate immune response to a variety of infectious microorganisms. They also link to the adaptive immune response through their induction of maturation of dendritic cells (DC) during the early phase of an immune response when the frequency of Ag-specific T cells is very low. We observe that in the presence of Borrelia burgdorferi, synovial Vδ1 T cells from Lyme arthritis synovial fluid potently induce maturation of DC, including production of IL-12, and increased surface expression of CD40 and CD86. The activated DC are then able to stimulate the Vδ1 T cells to up-regulate CD25. Both of these processes are initiated primarily by Fas stimulation rather than CD40 activation of DC via high expression of Fas ligand by the Vδ1 T cells. DC are resistant to Fas-induced death due to expression of high levels of the Fas inhibitor c-FLIP. This effect serves to divert Fas-mediated signals from the caspase cascade to the ERK MAPK and NF-κB pathways. The findings affirm the importance of the interaction of certain T cell populations with DC during the early phases of the innate immune response. They also underscore the view that as levels of c-FLIP increase, Fas signaling can be diverted from induction of apoptosis to pathways leading to cell effector function.

Interleukin-2 and aging: Decreased interleukin-2 production in healthy older people does not correlate with reduced helper cell numbers or antibody response to influenza vaccine and is not corrected in vitro by Thymosin α1

The capacity of lymphocytes obtained from healthy young or old volunteers to produce interleukin-2 was measured and the results were compared with other measures of immune function. The in vitro effect of thymosin alpha 1 on interleukin-2 production was also measured. Interleukin-2 was lower in lymphocytes from the elderly, and individuals with low production also had lower proliferative responses in vitro to phytohemagglutinin. These individuals did not have a reduced helper T-cell number, abnormal ratio of helper to suppressor T-cells or reduced antibody production in response to vaccine. Thymosin alpha 1 did not have a consistent effect on interleukin-2 production.

Suppression by progesterone of nonspecific in vitro lymphocyte stimulation in mice as a mechanism for the enhancement of herpes simplex virus type 2 vaginal infection

The role of antibody, interferon, and cell-mediated immunity (CMI) were studied to determine the mechanisms for progesterone enhancement of vaginal herpes simplex virus type 2 (HSV 2) infection in mice. Three groups of mice were studied: nonpregnant control, pregnant, and nonpregnant progesterone-treated mice. Vaginal infection with HSV 2 did not elicit a neutralizing antibody or a systemic interferon response in any of the groups tested. Splenic lymphocytes from noninfected and infected mice were stimulated in vitro with a nonspecific T-cell mitogen concanavalin (Con A) to measure the proliferative phase of CMI in these groups of mice. No suppression of (3H) thymidine (3HTdR) uptake was found in the pregnant or nonpregnant, progesterone-treated animals as compared to nonpregnant control mice. When progesterone was added directly to the splenic lymphocytes and continuously present during Con A stimulation a statistically significant depression of 3HTdR incorporation was found. We concluded that progesterone depresses Con A stimulation of murine lymphocytes, but progesterone must be continuously present to do so.