PubMed Health⌕ Search

Biomedical subjects

B Kyewski

Publications and source records attributed to B Kyewski.

29 records · Page 2Linked to original sources

Recruitment and activation of tumor-specific immune T cells in situ. CD8+ cells predominate the secondary response in sponge matrices and exert both delayed-type hypersensitivity-like and cytotoxic T lymphocyte activity.

This study analyzes the involvement of CD4+ and CD8+ T cells in a secondary cellular immune response to the highly metastatic murine lymphoma ESb in situ. This tumor line expresses tumor-associated transplantation Ag which can induce protective immunity in vivo and specific CTL in vitro. In tumor-immune mice the injection of a tumor vaccine (x-irradiated ESb tumor cells) into s.c. implanted vascularized sponges resulted in the generation of a specific secondary immune response characterized by massive leukocyte recruitment and generation of strong CTL activity at the restimulation site. During the antitumor immune response the CD4+:CD8+ T cell ratio decreased significantly and specifically in the restimulated sponges. Depletion of CD8+ but not CD4+ T cells from the tumor immune mice before restimulation significantly reduced the delayed-type hypersensitivity-like response and totally blocked the generation of tumor-specific CTL activity in situ. Only a minority of the CD8+ immune T cells which predominated the secondary response in situ expressed IL-2R and lymph node homing receptors as detected by the mAb MEL-14.

Animals↗

Identical forms of the CD2 antigen expressed by mouse T and B lymphocytes.

A monoclonal antibody (12-15) reactive with the mouse CD2 was used to study the expression of the antigen in different lymphoid cell subsets. By two-color immunofluorescence using B or T cell-specific reagents and cell sorting in combination with biochemical analysis we provide evidence that the CD2 antigen is present on mouse B and T cells. The antigen is expressed by both subsets at similar density and appears to be biochemically indistinguishable.

Animals↗

CD4+ helper T cells are required for resistance to a highly metastatic murine tumor.

A role of CD4+ T helper cells in induction of tumor transplant rejection leading to complete regression of a highly metastatic DBA/2 mouse lymphoma was analyzed. Using an anti-CD4 monoclonal antibody (GK1.5) which eliminates T helper cells in vivo and in vitro, we found that CD4+ cells are required for tumor resistance in syngeneic DBA/2 mice or allogeneic but major histocompatibility complex-identical B10.D2 mice. In contrast, in allogeneic C57BL/6 mice tumor rejection was independent of CD4+ cells. An analogous requirement for immune CD4+ cells for in vitro induction of CD8+ tumor-specific cytotoxic T cells was found in these respective strains. The requirement for immune CD4+ cells in vitro could be replaced by recombinant interleukin 2. These results demonstrate a role of CD4+ regulatory T cells and T-T cell cooperation in the induction of anti-tumor immunity and tumor rejection, and point to possible therapeutic interventions in the afferent phase of anti-tumor immune responses.

Animals↗

Composition of the lymphoid cell populations from omental milky spots during the immune response in C57BL/Ka mice.

The lymphoid cell composition of milky spots was analyzed in unprimed mice before and after i.p. immunization with sheep red blood cells. Milky spots contained surface immunoglobulin-positive B lymphocytes, and T cells of the helper and cytotoxic phenotype. After secondary antigen challenge the number of lymphocytes increased up to 40-fold, B and T cells were found to segregate into distinct areas in situ, and lymphocytes were found to associate with I-A-negative stromal cells in vivo. These findings qualify milky spots as a peripheral lymphoid organ exhibiting a remarkable change in number and composition of lymphocytes in response to a local antigen stimulus.

Animals↗

Autoimmune interaction measured in a postlabelling microcytostasis assay.

A postlabelling microcytostasis assay was developed to assess primary immune interaction between normal rat lymphocytes and autologous testis cells. In this vitro model of experimental autoimmune orchitis (EAO) unprimed T cells respond to a Sertoli-like subpopulation of testis cells during a 4 day culture period. The T effector cells exert a cytostatic effect on the monolayer-forming target cells. The number of remaining target cells, which inversely correlates with the intensity of the autoimmune reaction, is quantified by 51Cr incorporation. The assay is performed in multiple well plastic plates which allow rapid harvesting by cutting off the bottoms of each well. The attached labelled target cells are directly measured on the bottoms without any further transfer step. The method is adapted for the EAO model but may be useful to study primary T cell interaction with any other monolayer-forming target cells.

Animals↗