Measles virus (MV) suppresses specific functions in cells of the immune system and causes a generalized immunosuppression by mechanisms which remain undefined. It has been previously established that mitogen-induced proliferation of peripheral blood mononuclear cells (PBMC) is suppressed by infection with MV. Our current study demonstrates that MV infection inhibits antigen-specific proliferation of T lymphocytes. The inhibition of proliferation was not due to a decrease in IL-2 production. IL-2 production in cultures of infected and uninfected antigen-specific T cells was similar. In contrast, we found that expression of the IL-2R alpha subunit was decreased in mitogen-stimulated, MV-infected PBMC and antigen-stimulated, MV-infected T lymphocytes compared to stimulated but noninfected T cells. However, the expression of the IL-2R beta subunit was not altered in MV-infected T cells. We also examined the influence of MV infection on the production of the cytokines IL-4, IL-6, IL-10, and IFN-gamma by T lymphocytes. By comparing infected versus uninfected antigen-specific T cell lines, we found that MV infection of antigen-specific activated T cells caused no substantial change in generation of IFN-gamma, IL-6, or IL-10. There was a 50% reduction in IL-4 generation following MV infection. These data indicate that the immunosuppression by acute MV infection is not associated with a generalized inhibition of cytokine production. One mechanism for the suppression of proliferation following acute MV infection may be a block in the expression of the IL-2R alpha subunit by activated T cells.

Endogenous expression of antisense RNA in transfected cells has been explored for use in blocking cellular gene expression and for its antiviral potential. Antisense strategies were used with the goal of blocking measles virus (MV) infection. A recombinant expression plasmid was designed to produce antisense oligonucleotides targeted to the 5' end of the MV nucleocapsid protein mRNA. This construct was transfected into HeLa cells. The transfected cell line and a control cell line expressing a random RNA comprising the same nucleotides were infected with MV and assessed for viral resistance by observation of cytopathic effect (CPE); infectious virus was quantified by viral plaque assay. Both cell lines were also infected with a related paramyxovirus, mumps virus, as a specificity control. Both CPE and infectious virus were reduced by approximately 90% in the antisense-expressing line compared with that in control cells or transfectant cells expressing random RNA. There was no evidence of resistance to infection with mumps virus in any cell line.

The screening of a rat mast cell cDNA library with a probe selected to recognize those genes preferentially or exclusively expressed by mast cells identified a rat gene sequence, RF-17, that shared homology with the beta-integrins. This integrin was expressed in rat tissues enriched for mast cells and T cells. The rat RF-17 sequence was used to isolate the murine homologue from a spleen cDNA library. The murine gene encodes a protein of 806 amino acids that is the probable homologue to the human beta 7 chain. Transcripts specific for the murine gene are found in the thymus, spleen, and lung. To attempt to identify the gene product for this new integrin chain, we examined the murine T cell line TK-1, which expresses a novel integrin heterodimer, lymphocyte Peyer's patch high endothelial venule adhesion molecule (LPAM-1), of a known alpha 4 chain and an unknown beta P chain, for expression of murine beta 7 (RF-17). This cell line expresses high levels of RF-17 transcripts, suggesting that beta P is encoded by the beta 7 gene. Bone marrow cells induced to differentiate into mast cells via IL-3 express the beta 7 gene as well as the genes encoding the murine integrin alpha 4 and beta 1 proteins. Surface staining analysis indicates that these cells express an alpha 4-containing integrin complex throughout the differentiation process. These data suggest that the Peyer's patch homing LPAM-1 receptor expressed by a subset of T cells consists of the beta 7 gene product and the alpha 4 chain, and that this integrin chain complex is also found on the surface of maturing mast cells. The presence of beta 1 transcripts also suggests that these maturing mast cells possess the LPAM-2 integrin complex (alpha 4/beta 1) as well. The experimental strategy described in this manuscript has, thus, identified a novel murine beta-integrin chain that is expressed by rodent T cells and mast cells.