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R B Effros

Publications and source records attributed to R B Effros.

50 records · Page 3Linked to original sources
PubMed1983

Strong HLA-DR expression in T cell cultures after activation is necessary for IL-2-dependent proliferation.

We have examined the appearance of DR antigens on human T cells activated by PHA, using a monoclonal anti-DR framework antibody and a large panel of human HLA typing sera. Strong DR expression within the culture by day 8 was associated with the ability of cells to grow for long periods in IL-2 containing medium, whereas weak or absent DR expression was predictive of poor in vitro growth. All the cells responded equivalently to initial stimulation with PHA. These data support the hypothesis proposed by Moretta et al. to explain blocking of IL-2-dependent proliferation by an anti-DR antibody--that DR molecules may be involved in the transmission of signals by IL-2.

Cells, Cultured↗
PubMed1983

Diminished T-cell response to influenza virus in aged mice.

Declining immunity in aged individuals has been repeatedly verified. However, many of the studies have focused on functions not directly relevant to the antigens normally encountered in vivo. For example, although infectious agents represent a significant cause of morbidity and mortality in the elderly, age-related immune responses in such diseases have received very little experimental attention. The present study was, therefore, initiated to examine T cell-mediated immunity to influenza virus in aged mice. We observed that the primary cytotoxic T lymphocyte (CTL) response to influenza, which peaks at day 5 in young adult mice, is almost completely absent at that timepoint in aged mice. Our experiments indicate that the kinetics of the response are shifted, so that the maximum activity appears at days 7-9. Furthermore, a comparison of the peak responses of both age groups reveals a significantly lower magnitude in the aged mice. The diminished response was also observed for most of the old mice when antigenic stimulation occurred in vitro. Although the overall response was diminished, the characteristic T cell cross-reactivity for all A strain viruses was similar to that observed in young mice. The possible causes and consequences of the age-related decline in influenza-specific CTL activity are discussed.

Aging↗
PubMed1980

A "nonidiotypic" inhibition of influenza-immune H-2-restricted CTL by an anti-T cell serum.

A xenogeneic serum directed at alloimmune CTL is shown to block H-2-restricted anti-viral CTL activity. Extensive absorption studies with targets and effector cells indicate that the blocking is at the level of the CTL and not the target cells. Inhibition is demonstrated for influenza-specific cytotoxicity operating in the context of 3 distinct H-2 haplotypes, suggesting that the serum is not directed at antigen-recognition structures. Kinetic studies on the addition of RAT to an ongoing 51Cr release assay further support the hypothesis that inhibition is not operating via the idiotypic region of the antigen receptor. We suggest that RAT is specific for CTL surface structures involved in nonrecognition events--possibly the lytic sites or a conserved region (idiotype-negative) of th antigen-binding receptor.

Animals↗
PubMed1979

Inhibition of influenza-immune T cell effector function by virus-specific hybridoma antibody.

The in vitro activity of influenza-specific cytotoxic T cells can be inhibited by incubation of the target cells with monoclonal anti-influenza antibodies. Hybridoma antibodies that bind to the virus HA inhibit the cytotoxic activity of TDL for the virus-infected target by as much as 80%, whereas these same antibodies never reduce splenic T cell function by more than 40%. This reflects the fact that TDL from anti-influenza strain A/WSN/33 (HON1) are highly subtype-specific, whereas splenic effector cells from the same mice are cross-reactive for target cells infected with heterologous influenza A viruses. These findings are discussed in the light of previous failures to block virus-immune T cell effector function with heterogeneous antisera produced in vivo, and are considered to favor the idea that at least some of the "virus-immune" T cells are indeed recognizing viral antigens.

Animals↗
PubMed1979

A monoclonal antibody to viral glycoprotein blocks virus-immune effector T cells operating at H-2Dd but not at H-2Kd1.

A particular monoclonal antibody that binds to the influenza virus HA molecule inhibits HA-specific thymus-derived lymphocytes mediating cytotoxicity in the context of H-2Dd but not of H-2Kd. Another monoclonal antibody blocks both sets of HA-specific effector T cells. This observation, together with related findings from other laboratories, is considered to support the idea that T cell recognition is directed against some association of viral and H-2 glycoproteins, as proposed in the original formulation of the "altered self" concept.

Animals↗
PubMed1978

Influenzal pneumonia: early appearance of cross-reactive T cells in lungs of mice primed with heterologous type A viruses.

Mice were first primed with a type A or a type B influenza virus and then challenged intranasally at least 1 month later with another type A virus. Potent cytotoxic T cell populations were found in lung, and effector T cell function was also demonstrated in blood, spleen and mediastinal lymph nodes. Lymphocytes isolated from all of these anatomical sites were active against target cells infected with the same, or with serologically different, type A influenza viruses. Also, prior exposure to another type A virus resulted in more rapid development of effector function than was seen in mice that had first been infected with B/Lee. Cytotoxic T cell populations generated in mice with influenza thus tend overall to be type-specific, and there is substantial localization of these effector lymphocytes in the pneumonic lung.

Animals↗
PubMed1977

Induction of virus-specific modifications recognized by cytotoxic T cells is not altered by prior substitution of target cells with trinitrophenol.

Cytotoxic thymus-derived lymphocytes generated after interaction with trinitrophenyl (TNP)-substituted or virus-infected cells only lyse H-2 compatible target cells modified with the component used to immunize (TNP or virus). Prior saturation of TNP-reactive sites inhibits neither the infectivity of influenza A viruses, nor the capacity of infected cells to develop antigenic changes recognized by influenza-immune T cells. The two antigens are distinct entities on the cell membrane and do not obviously compete to form interactions with H-2 molecules.

Animals↗
PubMed1977

Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses.

Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses. T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity. Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents. This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus. The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses. However, not all of the virus-immune T-cell clones are cross-reactive. Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus. Even so, the less specific component is significant. Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus.

Animals↗
PubMed1977

Heterogeneity of the cytotoxic response of thymus-derived lymphocytes after immunization with influenza viruses.

Immunization of mice with serologically distinct type A influenza viruses results in development of highly crossreactive populations of cytotoxic thymus-derived lymphocytes (T cells). This can be shown both at the level of effector function and of priming for an enhanced response after challenge with another type A virus. Cytotoxic activity is demonstrable, in both the primary and secondary situations, only for H-2 compatible interactions. Further analysis by competitive inhibition experiments indicates that some of the T cell clones generated are specific for the virus used to immunize, while others are much less restricted. Secondary stimulation may result in preferential stimulation of the crossreactive T cells if the type A viruses used are very different serologically. When more closely related viruses are used, however, some degree of specificity is seen for the challenge virus. Even so, the patterns of crossreactivity observed are complex, and cannot be readily predicted on the basis of known serological relationships between surface hemagglutinin and neuraminidase antigens of type A influenza viruses.

Animals↗
PubMedDate not supplied

Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence.

The dramatic decline in immune function with age, especially in T cell proliferative activity, has been documented extensively in experimental animal models and in clinical studies of the elderly. A similar proliferative decline is also seen in long-term T lymphocyte cultures used to study in vitro cellular senescence. We have compared the peripheral blood T lymphocytes of centenarians and younger controls for the cell surface expression of CD28, a costimulatory molecule that is required for optimal activation and proliferation following engagement of the T cell receptor. Our analysis shows a significant decrease (p < 0.001) in the percentage of T cells expressing CD28 in the elderly cohort, with values ranging from 44% to 90%, as compared to the mean control value of 91%. The decline in the percentage of CD28+ T cells correlates with a reduction in the CD4/CD8 ratio (r2 = 0.695, p < 0.0001). Concommitantly, experiments using an in vitro T cell culture system showed a progressive loss of CD28 expression with culture "age." The concordance of proliferative decline and loss of CD28 in the centenarians and in the in vitro cultures suggest that a Hayflick phenomenon may operate in vivo leading to immunosenescence.

Adult↗
PubMedDate not supplied

Insights on immunological aging derived from the T lymphocyte cellular senescence model.

A human T cell culture system has been developed to study cellular senescence in a manner analogous to that used for fibroblasts. Using this system, several markers of replicative senescence have been identified. Evidence is provided to show that new insights into the immune deficiency of aging as well as HIV infection have emerged from the in vitro model. The culture model is now being exploited to dissect the basic mechanisms underlying the senescence program in T cells.

Animals↗
PubMedDate not supplied

Loss of CD28 expression on T lymphocytes: a marker of replicative senescence.

The CD28 molecule, a disulfide-linked homodimer expressed on peripheral T cells and thymocytes, mediates an essential costimulatory signal following engagement of the T cell receptor (TCR). Increased proportions of CD28- T cells have been observed during aging and in situations of chronic immune stimulation, but the origin and functional characteristics of these cells have been unclear. T cells which reach replicative senescence in culture after multiple rounds of cell division have shortened telomeres, respond poorly to stress stimuli, and no longer express CD28, suggesting that CD28- T cells observed in vivo may be the progeny of memory cells which have been repeatedly stimulated. This review describes the features of T cell replicative senescence, presents several possible mechanisms for the generation of senescent T cells in vivo, and proposes that replicative senescence may explain immune exhaustion.

Biomarkers↗
PubMedDate not supplied

Telomere shortening in T cells correlates with Alzheimer's disease status.

Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, and therefore serve as markers of a cell's replicative history. In vivo, clonal expansion of T cells during immune responses to both foreign and autoantigens is associated with telomere shortening. To investigate possible immune alterations in Alzheimer's disease (AD) that might impact current vaccine-based therapeutic strategies, we analyzed telomere lengths in immune cell populations from AD patients. Our data show a significant telomere shortening in PBMC from AD versus controls (P=0.04). Importantly, telomere length of T cells, but not of B cells or monocytes, correlated with AD disease status, measured by Mini Mental Status Exam (MMSE) scores (P=0.025). T cell telomere length also inversely correlated with serum levels of the proinflammatory cytokine TNFalpha (a clinical marker of disease status), with the proportion of CD8+ T cells lacking expression of the CD28 costimulatory molecule, and with apoptosis. These findings suggest an immune involvement in AD pathogenesis.

Aged↗