The human anti-murine xenogeneic cytotoxic response. II. Activated murine antigen-presenting cells directly stimulate human T helper cells.
Generation of a human T cell anti-murine xenogeneic response has previously been shown to be dependent on presentation of murine Ag by human APC. We have undertaken a series of experiments to better delineate the cellular defects that prevent effective production of IL-2 by human T cells upon direct exposure to murine stimulator populations. It was found that although resting human T cells cannot respond effectively to resting murine APC, they can respond to activated murine stimulator populations. Such APC activation could be mediated by murine granulocyte-macrophage-CSF or LPS that were associated with increased expression of B7-2 on the xenogeneic stimulating cell populations. Blocking studies with Ab provided further evidence that costimulation through CD28 played a critical role in the stimulation of human T cells by activated murine-stimulator cells in the production of IL-2. These results demonstrate the usefulness of this xenogeneic system in understanding human T cell-APC interactions and defining minimally sufficient T cell activation requirements. They further delineate the cellular level of deficient activation in the xenogeneic stimulation of human T cells by murine cell populations, and identify the potential importance of CD28/CTLA4 and its ligands in xenogeneic responses. These observations and concepts have implications for clinical efforts in xenografting.
Lucas
P J
PJ
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Bare
C V
CV
Gress
R E
RE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D008070:Lipopolysaccharides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor