10 results
Search Results
2. Emergent Group Dynamics Governed by Regulatory Cells Produce a Robust Primary T Cell Response.
- Author
-
Kim, Peter, Lee, Peter, and Levy, Doron
- Subjects
- *
T cells , *ANTIGENS , *MATHEMATICAL models , *IMMUNE response , *LYMPHOCYTES - Abstract
The currently accepted paradigm for the primary T cell response is that effector T cells commit to autonomous developmental programs. This concept is based on several experiments that have demonstrated that the dynamics of a T cell response is largely determined shortly after antigen exposure and that T cell dynamics do not depend on the level and duration of antigen stimulation. Another experimental study has also shown that T cell responses are robust to variations in antigen-specific precursor frequency. Various mathematical models have corroborated the first result that programmed T cell responses are insensitive to the level of antigen stimulation. However, this paper proposes that programmed responses do not entirely explain the robustness of T cell dynamics to variations in precursor frequency. This work studies the hypothesis that the dynamics of a T cell response may also be governed by a feedback loop involving adaptive regulatory cells rather than by intrinsic developmental programs. We formulate two mathematical models based on T cell developmental programs. In one model, effector cells undergo a fixed number of divisions before dying. In the second model, effector cells live for a fixed time during which they may divide. The study of these models suggests that developmental programs are not sufficiently robust as they produce an immune response that directly scales with precursor frequencies. Consequently, we derive a third model based on the principle that adaptive regulatory T cells develop in the course of an immune response and suppress effector cells. Our simulations show that this feedback mechanism responds robustly over a range of at least four orders of magnitude of precursor frequencies. We conclude that the proliferation program paradigm does not entirely capture the observed robustness of T cell responses to variations in precursor frequency. We propose an alternative mechanism by which the primary T cell response is governed by an emergent group dynamic and not by individual T cell programs. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
3. Modelling the interaction of T-Cells, antigen presenting cells, and HIV-1 in vivo
- Author
-
Lou, Jie and Shao, Yiming
- Subjects
- *
T cells , *LYMPHOCYTES , *ANTIGENS , *IMMUNITY , *BIOLOGY - Abstract
Abstract: We develop and analyze a model for the interactions of T-cells, antigen presenting cells (APCs), and HIV-1. Our model consists of five components: APCs, resting helper T-cells, activated uninfected helper T-cells, activated and infected helper T-cells, and the free virus. We emphasize the impact of APCs during HIV infection and the cell-to-cell contact manner in the transference of HIV-1 in vivo. The existence and stability of the uninfected steady state and those of the infected steady states are discussed. The uniform persistence of the system is also obtained. As a novel approach, multiple exposures of HIV-1 are illustrated and discussed in the paper. Through numerical stimulations, we check the sensitivity of APCs and helper T-cells in impacting the infection outcome and obtain some relevant results. We also give the lowest infectioe dose for certain individuals. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
4. Regulation of T-cell activation in the lung: isolated lung T cells exhibit surface phenotypic characteristics of recent activation including down-modulated T-cell receptors, but are locked into the G0/G1 phase of the cell cycle.
- Author
-
Strickland, D., Kees, U. R., and Holt, P. G.
- Subjects
- *
T cells , *LUNGS , *IMMUNITY , *RESPIRATORY organs , *LYMPHOCYTES , *ANTIGENS , *MACROPHAGES - Abstract
Peripheral lung tissue contains large numbers of T cells, strategically located for immune surveillance at the blood-air interface. Given the intensity of antigenic exposure at this site, it is clear that local T-cell activation events require strict control, in order to maintain tissue homeostasis. How this control is achieved in this unique tissue microenvironment is unknown, and the present study sought to elucidate the process via detailed analysis of the surface phenotypic characteristics of freshly isolated lung T cells. We report below that these cells display typical characteristic of ‘postactivation’, notably elevated basal Ca2+ concentrations, down-modulated T-cell receptors, expression of Ia and ‘late’ activation antigens and concomitant CD4/CD8. However, levels of interleukin-2 receptor and CD2 expression were below those expected of ‘activated’ T-cell populations, and virtually all of the cells were found to be in the G0/G1 phases of the cell cycle. These properties bear a remarkable similarity to those of T cells activated in the presence of endogenous tissue (alveolar) macrophages from the lung (see accompanying paper). We hypothesize that they reflect the in vivo operation of an endogenous macrophage-mediated T-cell anergy-induction process, the function of which is to limit the local clonal expansion of T cells in peripheral lung tissue after in situ activation. [ABSTRACT FROM AUTHOR]
- Published
- 1996
- Full Text
- View/download PDF
5. The absence of delayed-type hypersensitivity reactivity in a syngeneic murine tumour system.
- Author
-
Los, G., De Weger, R. A., Mobertes, R. M., Van Loveren, H., Sakkers, R. J., and Den Otter, W.
- Subjects
- *
DELAYED hypersensitivity , *ANTIGENS , *SEROTONIN , *T cells , *LYMPH nodes , *LYMPHOCYTES , *LABORATORY mice , *IMMUNOSUPPRESSION - Abstract
In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24–48 hr after antigen challenge were preceeded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 routine turnout system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngencic turnout system, we have transferred lymph node, spleen lymphocytes and scram from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000–80,000 MW fraction, and a 120,000–190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000–80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. [ABSTRACT FROM AUTHOR]
- Published
- 1987
6. Desensitization <em>in vitro</em>: the role of T-suppressor cells, T-suppressor factor and T-acceptor cells in the inhibition of the passive transfer of contact sensitivity to picryl chloride by exposure to antigen <em>in vitro</em>.
- Author
-
M. Zembala, Asherson, G.L., Colizzi, V., and Watkins, Madeleine C.
- Subjects
- *
T cells , *LYMPHOCYTES , *IMMUNITY , *IMMUNOLOGY , *ANTIGENS , *LYMPH nodes , *SPLEEN - Abstract
This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cyr, ATx5), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5, ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]
- Published
- 1982
7. Identification of two suppressor factors induced by early pregnancy factor.
- Author
-
Rolfe, Barbara E., Cavanagh, Alice C., Quinn, Kathryn A., and Morton, Halle
- Subjects
- *
LYMPHOCYTES , *T cells , *ALLERGIES , *PREGNANCY , *CONTACT dermatitis , *ANTIGENS - Abstract
The binding of EPF to lymphocytes stimulates the release of soluble mediators, active in T cell dependent reactions, namely the rosette inhibition test and the adoptive transfer of contact sensitivity. On the basis of their ability to inhibit the delayed type hypersensitivity reaction in this latter assay, they have been classified as suppressor factors. This paper describes the identification of two EPF-induced suppressor factors. Unlike EPF which is neither species-restricted nor strain-restricted, these factors are genetically restricted in their action in the rosette inhibition test EPF-S1 (estimated Mr 14,000) is restricted to the I region of the mouse MHC, while EPF-S2 (estimated Mr 55,000) is restricted to a locus (or loci) outside the MHC. Like other antigen non-specific factors, release of these suppressor factors can be stimulated also by Con A. [ABSTRACT FROM AUTHOR]
- Published
- 1988
8. Generation of non-MHC restricted killing in cultures stimulated with B cells from chronic lymphocytic leukaemia patients: phenotypic characterization of the precursor and effector cells.
- Author
-
Matera, Lina, Foa, R., Malavaski, F., Bellone, Graziella, Funaro, Ada, Veglia, F., and Santoli, Daniela
- Subjects
- *
LYMPHOCYTIC leukemia , *B cells , *LYMPHOCYTES , *CHRONIC diseases , *ANTIGENS , *T cells - Abstract
Freshly isolated B cells from chronic lymphocytic leukaemia patients (B-CLL) have been previously shown to induce a strong proliferative response and high levels of NK-like activity in lymphocytes from healthy donors. The present paper deals with the origin, mitotic state, target spectrum and cell surface phenotype of the NK-like effectors generated after stimulation with B-CLL. Experiments using large granular lymphocytes (LGL) and T cells as responders demonstrated that most of the precursors of the newly generated NK-like effectors express the CD3 antigen. The induction of NK-like activity paralleled cell activation, as judged by blast transformation, thymidine uptake and appearance of cell surface activation markers. The newly generated NK-like effectors displayed a T cell phenotype and a broader target repertoire than native NK cells. [ABSTRACT FROM AUTHOR]
- Published
- 1988
9. Regulation of the immune response in Plasmodium falciparum malaria II. Antigen specific proliferative responses in vitro.
- Author
-
Troye-Blomberg, Marita, Perlmann, Hedvig, Patarroyo, M. E., and Perlmann, P.
- Subjects
- *
DNA synthesis , *PLASMODIUM falciparum , *LYMPHOCYTES , *IMMUNOGLOBULINS , *T cells , *ANTIGENS - Abstract
The antigen-induced DNA synthesis in vitro in lymphocytes from patients with acute Plasmodium falciparum malaria was investigated. The patients and healthy controls from Sweden or Colombia were the same as those studied in the accompanying paper (Troye-Blomberg el al., 1983). The malarial antigens used were sonicated membrane preparations or purified and concentrated supernatants from in vitro cultures of P. facliparum, similar preparations derived from normal human erythrocytes served as control antigen. In the patients' lymphocytes P. falciparum antigens induced a weak or moderate but significant stimulation of DNA synthesis, peaking after 3-4 days of incubation. This early response was specific for P. faleiparum since it was not obtained with lymphocytes from healthy donors nor with those from patients with acute P. vivax or P. ovale malaria. No antigen-induced response was seen in about half of the P.falciparum patients. However in a few negative eases, available for consecutive testing, positive reactions were seen with lymphocytes taken 2 weeks after infection when the blood of these patients was free of parasites. The early response induced in patients' lymphocytes to the P. falciparum antigens was not obtained with RBC antigen, however, these preparations frequently induced a response rising to significant levels later during incubation (day 5-6)- Similar delayed responses were obtained when either- patients' or control donors' lymphocytes were exposed to the P. falciparum antigens. This indicates that both the RBC and the parasite preparations contained mitogenic substances affecting human lymphocytes in general and easily obscuring the P, falciparum specific responses seen only in the patients. This latter response was relatively low and short lived, suggesting that it reflected a secondary in vitro stimulation of in vivo primed lymphocytes and that it was regulated by suppressor mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 1983
10. Absence of any male-specific antigen recognized by T lymphocytes in X/X<em>Sxr′</em> male mice.
- Author
-
McLaren, A., Hunt, R., and Simpson, E.
- Subjects
- *
CHROMOSOMES , *LYMPHOCYTES , *T cells , *TRANSPLANTATION immunology , *GRAFT rejection , *ANTIGENS - Abstract
Previous work has established that whereas X/X mice carrying the sex-reversing chromosomal fragment Sxr are positive for the male-specific transplantation antigen, H-Y, X/X mice carrying the variant Sxr', although they too develop as phenotypic males, are H-Y negative. In this paper we show that X/XSxr' male mice do not express any male-specific antigen that can induce skin-graft rejection. [ABSTRACT FROM AUTHOR]
- Published
- 1988
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.