In Vivo Collaboration between Precursor T Cells and Helper T Cells in the Development of Delayed-Type Hypersensitivity Reaction to Influenza Virus in Mice

1982 ◽  
Vol 16 (3) ◽  
pp. 257-264 ◽  
Author(s):  
K. N. LEUNG ◽  
E. SCHILTKNECHT ◽  
G. L. ADA
2008 ◽  
Vol 253 (1-2) ◽  
pp. 110-115 ◽  
Author(s):  
Friderike Blumenthal-Barby ◽  
Arnhild Schrage ◽  
Katharina Eulenburg ◽  
Martin Zeitz ◽  
Alf Hamann ◽  
...  

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2869-2874 ◽  
Author(s):  
Takayuki Yoshimoto ◽  
Chrong-Reen Wang ◽  
Toshihiko Yoneto ◽  
Akio Matsuzawa ◽  
William W. Cruikshank ◽  
...  

Interleukin (IL)-16 is a chemoattractant cytokine for CD4+ leukocytes. Because delayed-type hypersensitivity (DTH) reaction is mediated by T helper 1 (Th1) cells and CD4+ T cells can be chemoattracted by IL-16, we have investigated the involvement of IL-16 in the DTH reaction. Immunohistochemical analysis revealed the IL-16 expression in infiltrating cells and epithelial cells in the DTH footpads. The IL-16 expression was also detected intracellularly in the infiltrating cells. In addition, markedly increased production of IL-16 was detected in the DTH footpad extracts, but not in the control footpad extracts, by an enzyme-linked immunosorbent assay and also by Western blot analysis. The DTH footpad extracts exhibited a strong chemoattractant activity toward splenic T cells, which was significantly inhibited by the inclusion of neutralizing monoclonal antibody (mAb) against IL-16 in the migration assay. Furthermore, treatment of sensitized mice in vivo with the anti-IL-16 neutralizing mAb significantly suppressed the footpad swelling induced by an antigen challenge, together with decreased infiltration of leukocytes including not only CD4+ T cells but also CD8+ T cells and macrophages into the DTH footpads. Decreased production of macrophage inflammatory protein 1 was also observed in the DTH footpad extracts by the mAb treatment. These results suggest that IL-16 plays an important role in the recruitment of leukocytes—presumably including antigen-specific Th1 cells, which secrete cytokines and chemokines mediating the following hypersensitivity reaction after activation by the interaction with Langerhans cells carrying the antigen—for the elicitation of DTH response.


1981 ◽  
Vol 153 (5) ◽  
pp. 1029-1043 ◽  
Author(s):  
K N Leung ◽  
G L Ada

Injection of mice with infectious or noninfectious preparations of influenza virus induces the formation of T cells which, when added to primary tissue cultures of normal spleen cells exposed to influenza virus, enhance the generation of effector T cells which mediate delayed-type hypersensitivity (DTH) reaction. The enhancing cells possess Thy-1 and Ly-1 surface antigens are radioresistant and antigen-specific. If infectious virus was used to stimulate the DTH response in vitro, help was delivered whether homologous or heterologous A strain influenza virus was used to generate the helper T cells (Th) in vivo. In contrast, only Th cells generated using homologous virus were effective if noninfectious virus was used to stimulate the DTH response in vitro. Peak helper activity occurred 2 d after virus injection and the Th cells were only effective if added to the primary cultures within 24 h after addition of the stimulating antigen. The Th cells enhanced the generation of both classes of DTH effector cells, i.e., those that are Ly-1 positive and IA-subregion restricted and those that are Ly-2,3 positive and K,D-region restricted. The activity of the Th cells was found to be IA-subregion restricted and this was shown to operate at the level of the stimulator cells so that the delivery of help to the responder cells was not H-2 restricted. The possibility that the Th cells might be a precursor to the Ly-1 positive IA subregion-restricted DTH effector cells is discussed.


1976 ◽  
Vol 144 (3) ◽  
pp. 776-787 ◽  
Author(s):  
R M Zinkernagel

In mice, primary footpad swelling after local infection with lymphocytic choriomeningitis virus (LCMV) and delayed-type hypersensitivity (DTH) adoptively transferred by LCMV immune lymphocytes are T-cell dependent. Nude mice do not develop primary footpad swelling, and T-cell depletion abrogates the capacity to transfer LCMV-specific DTH. Effector T cells involved in eliciting dose-dependent DTH are virus specific in that vaccinia virus-immune lymphocytes could not elicit DTH in LCMV-infected mice. The adoptive transfer of DTH is restricted to H-2K or H-2D compatible donor-recipient combinations. Distinct from the fowl-gamma-globulin DTH model, I-region compatibility is neither necessary nor alone sufficient. Whatever the mechanisms involved in this K- or D-region associated restriction in vivo, it most likely operates at the level of T-cell recognition of "altered self" coded in K or D. T cells associated with the I region (helper T cells and DTH-T cells to fowl-gamma-globulin) are specific for soluble, defined, and inert antigens. T cells associated with the K and D region (T cells cytotoxic in vitro and in vivo for acute LCMV-infected cells, DTH effector T cells, and anti-viral T cells) are specific for infectious, multiplying virus. The fact that T-cell specificity is differentially linked with the I region or with the K and D regions of H-2 may reflect the fundamental biological differences of these antigens. Although it cannot be excluded that separate functional subclasses of T-effector cells could have self-recognizers for different cell surface structures coded in I or K and D, it is more likely that the antigen parameters determine whether T cells are specific for "altered" I or "altered" K- or D-coded structures.


1981 ◽  
Vol 154 (1) ◽  
pp. 24-34 ◽  
Author(s):  
G G Miller ◽  
P I Nadler ◽  
Y Asano ◽  
R J Hodes ◽  
D H Sachs

Treatment of BALB/c mice with purified pig anti-(BALB/c anti-nuclease) anti-idiotypic antibodies has been found to induce the appearance of idiotype-bearing immunoglobulins (Id') in the serum of these mice in the absence of detectable antigen binding activity. This phenomenon appeared to require T cells in the hosts because no Id' was detected in the serum of nude mice similarly treated. Furthermore, the spleens of BALB/c mice treated with anti-idiotype were found to contain helper T cells capable of providing help in an in vitro plaque-forming cell response to trinitrophenyl-nuclease equivalent to that provided by helper T cells from the spleens of nuclease-primed animals. Helper T cells from both anti-idiotype-treated and nuclease-treated animals were found to be antigen-specific and to be similarly susceptible to elimination by treatment with anti-idiotype plus complement. Therefore, treatment with both antigen and anti-idiotype appeared to prime similar populations of antigen-specific helper T cells, while having different effects on the induction of antibody. These findings are consistent with the network theory of receptor interactions in the immune response, and may provide a means for studying individual cell populations involved in such interactions.


Immunity ◽  
2002 ◽  
Vol 17 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Daniel B Stetson ◽  
Markus Mohrs ◽  
Valerie Mallet-Designe ◽  
Luc Teyton ◽  
Richard M Locksley

1997 ◽  
Vol 185 (12) ◽  
pp. 2133-2141 ◽  
Author(s):  
Elizabeth Ingulli ◽  
Anna Mondino ◽  
Alexander Khoruts ◽  
Marc K. Jenkins

Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific T cells has never been directly observed in vivo under conditions where the specificity of the responding T cells for the relevant antigen could be unambiguously assessed. We used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4+ T cells specific for an OVA peptide–I-Ad complex after adoptive transfer into syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell–rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.


1989 ◽  
Vol 169 (2) ◽  
pp. 535-548 ◽  
Author(s):  
H Rosen ◽  
G Milon ◽  
S Gordon

We have used the delayed-type hypersensitivity (DTH) response to SRBC or tuberculin to examine the role of the murine type 3 complement receptor in T lymphocyte-dependent inflammatory recruitment. Intravenous injection of 5C6, a CR3-specific rat mAb known to impair myelomonocytic adhesion, divided the DTH to SRBC in actively immunized mice into two phases. The early phase, which lasted 24 h, was characterized by maximal oedema and maximal inflammatory recruitment and was 5C6 inhibitable. The later phase was 5C6 resistant and reached a peak 48 h after antigenic challenge and was superimposable on the declining peak seen in control mice. Passive transfer of reactive T cells mixed with antigen was used to examine the myelomonocytic effector arm of the DTH alone. Both passive transfer of cutaneous DTH to SRBC and passive transfer of the largely monocytic T cell-dependent recruitment to tuberculin in the peritoneal cavity were completely abolished by systemic 5C6 treatment. Injection of 5C6-treated donor leukocytes at the site of passive transfer had no effect. Treatment of donor mice with 5C6 at the time of active immunization did not alter their ability to provide reactive T cells for passive transfer. The myelomonocyte-restricted rat mAb 7/4 and the rapidly cleared F(ab')2 fragment of 5C6 showed no inhibition of the DTH. In all cases, inhibition of footpad swelling correlated with histological evidence of inhibition of myelomonocytic cell recruitment. Peritoneal cell counts after local DTH to tuberculin showed complete inhibition of monocyte recruitment. We conclude that CR3 plays a quantitatively important role in T cell-dependent inflammatory recruitment. This is absolute in passive transfer experiments, but only partial after active immunization. Leukocyte CR3 plays a common role in both immunologically specific and nonspecific inflammatory recruitment and provides a target that could possibly be manipulated to therapeutic advantage.


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