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.

Abstract

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.

Direct intralymphatic injection of peptide vaccines enhances immunogenicity

“…EL-4 cells were pulsed with 10 -6 M gp33 for 2 h or left untreated. 51 Cr-release assays were performed according to standard protocols [17] at the indicated E/T ratios. Incubation time was 5 h. Specific lysis was calculated as (experimental cpm -spontaneous cpm)/ (total cpm -spontaneous cpm).…”

Marginal Zone Macrophages and Immune Responses Against Viruses

“…with LCMV. After footpad infection, immunocompetent mice develop a footpad swelling reaction due to a biphasic CD8 ϩ and CD4 ϩ T cell response (29,33). The strength and the kinetics of the swelling reaction correlate with the induction and recruitment of T cells to the site of infection.…”

“…The footpad thickness was measured with a spring-loaded caliper (Kroeplein; Schluchtern, Hessen, Germany). Values were taken as the mean of both hind footpads (29,33).…”

“…The cytolytic activity of spleen cells was tested in a 51 Cr release assay as described previously (29). Briefly, EL-4 target cells were coated with LCMV-derived peptide gp33-41 (30) at concentrations of 10 Ϫ6 M. A total of 10 4 target cells were incubated in 96-well round-bottom plates with serial 3-fold dilutions of spleen effector cells starting at an E:T ratio of 70:1 in a final volume of 200 l. After 5 h of incubation at 37°C, 70 l of supernatant was harvested and radioactivity determined in a gamma counter, and the percentage of specific release was calculated.…”

Murine candidiasis: Susceptibility is associated with the induction of T cell‐mediated, strain‐specific autoreactivity

“…T cell-mediated immune responses are controlled directly by MHC genes, and in diseases such as lymphocytic choriomeningitis virus infection, the severity of the disease shows a strong correlation with the magnitude of cell-mediated immune responses (1,2). In other infections in which the immunopathological component is not as strong, the severity of tissue lesions appears to be determined by innate resistance mechanisms that are controlled by non-MHC genes (3).…”