scholarly journals Delayed Clearance of Ehrlichia chaffeensis Infection in CD4+ T-Cell Knockout Mice†

2004 ◽  
Vol 72 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Roman R. Ganta ◽  
Chuanmin Cheng ◽  
Melinda J. Wilkerson ◽  
Stephen K. Chapes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Cell Mediated Immunity ◽  
Ehrlichia Chaffeensis ◽  
Wild Type

ABSTRACT Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. To examine the role of helper T cells in host resistance to this macrophage-tropic bacterium, we assessed E. chaffeensis infections in three mouse strains with differing functional levels of helper T cells. Wild-type, C57BL/6J mice resolved infections in approximately 2 weeks. Major histocompatibility complex class II (MHCII) knockout, B6.129-Abb tm1 mice lacking helper T cells developed persistent infections that were not resolved even after several months. CD4+ T-cell-deficient, B6.129S6-Cd4 tm1Knw mice cleared the infection, but the clearance took 2 weeks longer than it did for wild-type mice. C57BL/6J mice resolved infection more rapidly following a second experimental challenge, but B6.129S6-Cd4 tm1Knw mice did not. The B6.129S6-Cd4 tm1Knw mice also developed active E. chaffeensis-specific immunoglobulin G responses that were slightly lower in concentration and slower to develop than that observed in C57BL/6J mice. E. chaffeensis-specific cytotoxic T cells were not detected following a single bacterial challenge in any mouse strain, including wild-type C57BL/6J mice. However, the cytotoxic T-cell activity developed in all three mouse strains, including the MHCII and CD4+ T-cell knockouts, when challenged with a second E. chaffeensis infection. The data reported here suggest that the cell-mediated immunity, orchestrated by CD4+ T cells is critical for conferring rapid clearance of E. chaffeensis.

scholarly journals In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors.

1978 ◽  
Vol 148 (6) ◽  
pp. 1579-1591 ◽  
Author(s):  
L L Baum ◽  
L M Pilarski
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Helper Cell ◽  
Cytotoxic T Cell ◽  
Spleen Cells

Antigen-specific helper T cells are required in the generation of cytotoxic T cells from thymocyte precursors. We have demonstrated that these alloantigen-specific helper cells can be generated in vitro and that both the quantity and quality of the helpers appear to be superior to the help obtained from unprimed spleen cells. Optimal helper cell activity is produced at day two of culture when CBA splenic helper precursors are stimulated by irradiated allogeneic spleen cells. Helper cell precursors are antigen-specific cells which cannot be instructed to express forbidden receptor specificities and bear theta antigen on their surface. The helper effectors are radioresistant, theta-bearing, and antigen-specific cells.

scholarly journals The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help.

1978 ◽  
Vol 147 (3) ◽  
pp. 897-911 ◽  
Author(s):  
R M Zinkernagel ◽  
G N Callahan ◽  
A Althage ◽  
S Cooper ◽  
J W Streilein ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Phenotypic Expression ◽  
Cell Activity ◽  
Thymic Epithelial Cells ◽  
Cytotoxic T Cell ◽  
Immunological Interactions

The thymus determines the spectrum of the receptor specificities of differentiating T cells for self-H-2; however, the phenotypic expression of T cell's specificity for self plus virus is determined predominantly by the H-2 type of the antigen presenting cells of the peripheral lymphoreticular system. Furthermore, virus specific helper T cells are essential for the generation of virus-specific cytotoxic T cells. For cooperation between mature T cells and other lymphocytes to be functional in chimeras, thymic epithelial cells and lymphohemopoietic stem cells must share the I region; killer T-cell generation also requires in addition compatibility for at least one K or D region. These conclusions derive from the following experiments: A leads to (A X B)F1 chimeric lymphocytes do produce virus-specific cytotoxic T-cell activity for infected A but not for infected B cells; when sensitized in an acutely irradiated and infected recipient (A X B)F1 these chimeric lymphocytes respond to both infected A and B. Therefore the predominantly immunogenically infected cells of chimeras the radiosensitive and by donor stem cells replaced lymphoreticular cells. In this adoptive priming model (KAIA/DB leads to KAIA/DC) chimeric lymphocytes could be sensitized in irradiated and infected F1 against KA and DC but not against infected DB targets. In contrast KBIB/DA leads to KCIC/DA chimeras' lymphocytes could not be sensitized at all in appropriately irradiated and infected F1 recipients. Thus these latter chimeras probably lack functional I-specific T helper cells that are essential for the generation of T killer cells against infected D compatible targets. If T cells learn in the thymus to recognize H-21 or K, D markers that are not at least partially carried themselves in other cells of the lymphoreticular system immunological interactions will be impossible and this paradox situation results in phenotypic immune incompetence in vivo.

scholarly journals A requirement for antigen-specific helper T cells in the generation of cytotoxic T cells from thymocyte precursors.

1977 ◽  
Vol 145 (3) ◽  
pp. 709-725 ◽  
Author(s):  
L M Pilarski
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Third Party ◽  
Helper T Cells ◽  
Cytotoxic T Cell ◽  
Spleen Cells ◽  
Stimulator Cell ◽  
Effector Cells ◽  
Helper Cells

Thymocytes cultured with irradiated, allogeneic stimulator cells yield no cytotoxic effector cells after a period in culture. If, however, a population of irradiated spleen cells syngeneic to the responder cells are added to these cultures, cytotoxicity is generated. The helper activity present in the irradiated syngeneic spleen cells was found to be mediated by a cell bearing theta antigens. Furthermore, it was found to be antigen specific; helper cells which were tolerant of the stimulator cell antigens were unable to help the thymocyte responder cells, although these tolerant cells did contain helpers specific for a third party antigen. These experiments are consistent with a requirement for associative recognition of linked determinants in the induction of killer precursors which is thus strictly analogous to the induction of B-cell precursors via collaboration with helper T cells. In more extensive studies, it was found that histoincompatible helper cells (H-2b, H-2p, H-2q) were able to help a cytotoxic T cell (H-2k) response to a third party stimulator cell antigen (H-2d); that is, the helper T cells which interact with cytotoxic T-cell precursors are not strain specific. It seems likely that the histocompatible helper cells induce killer precursors in an antigen-specific cooperation event similar or identical to normal syngeneic cooperation.

Uncovering metabolic states in cytotoxic T cells, one cell at a time

2020 ◽  
Vol 12 (563) ◽  
pp. eabe6027
Author(s):  
Ioannis Zervantonakis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cytotoxic T Cells ◽  
Activity Patterns ◽  
Cell Activity ◽  
Cytotoxic T Cell ◽  
Colorectal Tumors ◽  
Metabolic State ◽  
Metabolic States

Single-cell metabolic state analysis reveals cytotoxic T cell activity patterns that are spatially organized in human colorectal tumors.

scholarly journals Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells.

1991 ◽  
Vol 174 (4) ◽  
pp. 891-900 ◽  
Author(s):  
S M Friedman ◽  
M K Crow ◽  
J R Tumang ◽  
M Tumang ◽  
Y Q Xu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Activity ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Mycoplasma Arthritidis ◽  
Human T Cells

While all known microbial superantigens are mitogenic for human peripheral blood lymphocytes (PBL), the functional response induced by Mycoplasma arthritidis-derived superantigen (MAM) is unique in that MAM stimulation of PBL consistently results in T cell-dependent B cell activation characterized by polyclonal IgM and IgG production. These immunostimulatory effects of MAM on the humoral arm of the human immune system warranted a more precise characterization of MAM-reactive human T cells. Using an uncloned MAM reactive human T cell line as immunogen, we have generated a monoclonal antibody (mAb) (termed C1) specific for the T cell receptor V beta gene expressed by the major fraction of MAM-reactive human T cells, V beta 17. In addition, a V beta 17- MAM-reactive T cell population exists, assessed by MAM, induced T cell proliferation and cytotoxic T cell activity. mAb C1 will be useful in characterizing the functional properties of V beta 17+ T cells and their potential role in autoimmune disease.

scholarly journals Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development

1977 ◽  
Vol 146 (1) ◽  
pp. 91-106 ◽  
Author(s):  
T Hamaoka ◽  
M Yoshizawa ◽  
H Yamamoto ◽  
M Kuroki ◽  
M Kitagawa
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Development ◽  
Cell Activity ◽  
Helper T Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Suppressor T Cell ◽  
Suppressor T Lymphocytes

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.

6 Murine T cell subsets and interleukins: Relationships between cytotoxic T cells, helper T cells and accessory cells

1982 ◽  
Vol 11 (3) ◽  
pp. 607-630
Author(s):  
Hermann Wagner ◽  
Martin Kronke ◽  
Werner Solbach ◽  
Peter Scheurich ◽  
Martin Röllinghoff ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
T Cell Subsets ◽  
Helper T Cells ◽  
Accessory Cells

scholarly journals Susceptibility to lymphocytic choriomeningitis virus isolates correlates directly with early and high cytotoxic T cell activity, as well as with footpad swelling reaction, and all three are regulated by H-2D.

1985 ◽  
Vol 162 (6) ◽  
pp. 2125-2141 ◽  
Author(s):  
R M Zinkernagel ◽  
T Leist ◽  
H Hengartner ◽  
A Althage
Keyword(s):  
T Cell ◽  
Virus Isolate ◽  
Cell Activity ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Time To Death ◽  
Virus Isolates ◽  
Susceptibility Patterns

The lymphocytic choriomeningitis virus (LCMV) isolates Docile (D) and Aggressive (A) of Pfau et al. were studied in various strains of mice. Disease susceptibility, assessed as mortality and time to death to LCMV-D or -A varied greatly amongst mouse strains, and all four possible susceptibility patterns were observed: susceptibility to both (e.g. SWR/J), resistance to both (e.g. DBA/2), susceptibility to A but resistance to D (C57BL/6), or vice versa (CBA/J). Irrespective of the virus isolate or the mouse strain tested, susceptibility correlated with both early and high cytotoxic T cell activity found in spleens or leptomeningeal infiltrates, and with early and high primary footpad swelling reaction after local infection. C57BL/6 mice infected with A or SWR/J infected with A or with D showed, in both test systems, early and high activities; in contrast, DBA/2 mice infected with either D or A, and C57BL/6 infected with D showed no or only slow and low responses in both tests. Early and high LCMV-specific cytotoxic T cell activity, and the rapidity and extent of the primary footpad reaction directly correlated with susceptibility to LCM and all were dominantly regulated by H-2D.

scholarly journals Protective Immunity against Experimental Pulmonary Cryptococcosis in T Cell-Depleted Mice

2011 ◽  
Vol 18 (5) ◽  
pp. 717-723 ◽  
Author(s):  
Karen L. Wozniak ◽  
Mattie L. Young ◽  
Floyd L. Wormley
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protective Immunity ◽  
Effector Memory ◽  
Cell Phenotype ◽  
Cell Mediated Immunity ◽  
Wild Type ◽  
Pulmonary Cryptococcosis ◽  
Content Type ◽  
Immunocompetent Mice

ABSTRACTIndividuals with defects in T cell-mediated immunity (CMI) are highly susceptible to infection withCryptococcus neoformans. The purpose of these studies was to determine if protection against experimental pulmonary cryptococcosis can be generated in T cell-deficient hosts. BALB/c mice were depleted of CD4+and/or CD8+T cells or given an isotype control antibody prior to vaccination with aC. neoformansstrain, designated H99γ, previously shown to induce protection againstC. neoformansinfection in immunocompetent mice. Mice depleted of CD4+or CD8+T cells, but not both subsets, survived an acute pulmonary infection withC. neoformansstrain H99γ and a subsequent second challenge with wild-typeC. neoformansstrain H99. We observed a significant increase in the percentage of CD4+and CD8+T cells expressing the activation marker CD69 in the lungs of mice immunized withC. neoformansstrain H99γ prior to a secondary challenge with wild-type cryptococci. CD4+T cells within the lungs of immunized mice also appeared to acquire a predominantly activated effector memory cell phenotype (CD69+CD44+CCR7−CD45RB−CD62L−) following a second pulmonary challenge with wild-typeC. neoformans, compared to CD4+T cells from naïve mice. Lastly, immunization of immunocompetent mice withC. neoformansstrain H99γ prior to depletion of CD4+and/or CD8+T cells resulted in significant protection against a second challenge with wild-typeC. neoformans. Our studies demonstrate that protective immunity against pulmonary cryptococcosis can be generated in immunosuppressed hosts, thus supporting the development of cryptococcal vaccines.

scholarly journals Allorestricted cytotoxic T cells. Large numbers of allo-H-2Kb-restricted antihapten and antiviral cytotoxic T cell populations clonally develop in vitro from murine splenic precursor T cells.

1985 ◽  
Vol 162 (2) ◽  
pp. 592-606 ◽  
Author(s):  
J Reimann ◽  
D Kabelitz ◽  
K Heeg ◽  
H Wagner
Keyword(s):  
T Cells ◽  
High Probability ◽  
Cytotoxic T Lymphocyte ◽  
Cytotoxic T Cells ◽  
Large Fraction ◽  
Cytotoxic T Cell ◽  
Wild Type ◽  
Large Numbers ◽  
Simplex Virus

Cytotoxic T lymphocyte (CTL) responses of splenic T cells from C57BL/6 B6) mice and mutant H-2Kbm1 (bm1) mice to haptenic (trinitrophenyl [TNP] ) and herpes simplex virus (HSV) determinants in the context of an allogenic (wild-type or mutant) H-2Kb molecule were analyzed in a modified limiting dilution system. In the B6-anti-bm1TNP mixed leukocyte reaction (MLR), estimated frequencies for precursors of CTL clones that lysed bm1TNP targets ranged from 1/120 to 1/400; in the bm1-anti-B6TNP MLR, estimated frequencies of precursors of CTL clones that lysed B6TNP targets ranged from 1/500 to 1/1,300. Estimated frequencies for precursors of CTL clones that lysed the respective unmodified and TNP-modified allogeneic targets were two- to three-fold lower. Lytic specificity patterns determined by split-well analysis showed that at least 20-30% of the generated CTL populations (selected for a high probability of clonality) in both MLR displayed allorestricted lysis of TNP-modified concanavalin A blast targets. In the B6-anti-bm1HSV MLR, estimated frequencies for precursors of CTL clones that lysed bm1HSV targets ranged from 1/70 to 1/300; in the bm1-anti-B6HSV MLR, estimated frequencies for precursors of CTL clones that lysed B6HSV targets ranged from 1/300 to 1/1,200. Again, estimated frequencies for precursors of CTL clones that lysed the respective noninfected and virus-infected allogeneic targets were two- to fourfold lower. Of the CTL populations selected for a high probability of clonality at least 30-60% displayed allorestricted lysis of virus-infected lipopolysaccharide blast targets in both MLR. It is concluded that a large fraction of clonally developing CTL populations stimulated with TNP-modified or HSV-infected allo-H-2Kb-bearing cells displayed an allorestricted pattern of recognition. It was further evident that the estimated frequencies of splenic precursors that generated allorestricted CTL clones was two- to threefold higher than the estimated frequencies of precursors that gave rise to the respective alloreactive CTL populations.

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