Virus specificity of cytotoxic T lymphocytes generated during acute lymphocytic choriomeningitis virus infection: role of the H-2 region in determining cross-reactivity for different lymphocytic choriomeningitis virus strains

100

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.

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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.

Zinkernagel¹,

Leist²,

Hengartner³

et al. 1985

100

“…CTL responses of both the H-2 b and H-2 a tg mice were effective and efficient in controlling LCMV infection. The CTL response to LCMV of H-2 b and H-2 d mice maps to genes (NP or GP) encoded by the S-RNA (16,(27)(28)(29)(30)(31)(32). The CTL response in H-2 b mice maps to both GP (aa 33-41 and aa 276-286) and NP (aa 396-404) proteins, whereas in H-2 d mice the CTL response maps only to a single immunodominant NP epitope, aa 118-127 (15,28).…”

Section: Discussionmentioning

confidence: 99%

Thymic selection and adaptability of cytotoxic T lymphocyte responses in transgenic mice expressing a viral protein in the thymus.

Herrath

Dockter

Nerenberg

et al. 1994

Self Cite

SummaryUpon primary challenge with lymphocytic choriomeningitis virus (LCMV), H-2 a (BALB/cByJ) mice mount a cytotoxic T lymphocyte (CTL) response to a single immunodominant domain of the viral nucleoprotein (NP) but no detectable response to the viral glycoprotein (GP). To manipulate this CTL response, the viral NP gene was expressed in the thymus and peripheral T lymphocytes using the murine Thyl.2 promoter. As a result, such Thyl.2-NP (H-2 a) transgenic (tg) mice deleted their high-affinity anti-I_CMV-NP CTL, but generated equal numbers of lower-affinity NP CTL. Further, they made an alternative anti-LCMV-GP CTL response that is not normally found in non-tg mice indicating a hierarchial control of the CTL response. Unlike the H-2 a mice, H-2 b (C57B1/6J) mice normally mount a CTL response to both LCMV-GP and -NP. When the LCMV-NP was expressed using the Thyl.2 promoter in these H-2 b mice, the LCMV-NP-specific CTL response was completely aborted and no CTL to new, alternative viral epitopes were generated. Dilutions of H-2 b or H-2 a NP peptides indicated that 3-4 logs less H-2 b NP peptide was required to sensitize syngeneic target cells for CTL-specific lysis, suggesting that the differing affinities of H-2 b and H-2 a major histocompatibility complex molecules for their peptides likely account for the total removal of NP CTL in the H-2 b mice but only partial removal in H-2 a mice made to express thymic NP. Thymic grafting experiments done with thymi from newborn Thyl.2-NP tg mice show that selection processes studied in this model are of central (thymic) origin and are not caused by Thyl.2-positive LCMV-NP-expressing T lymphocytes in the periphery.

“…Bacteria numbers were accurately confirmed by spreading bacteria samples onto brain-heart infusion plates plus erythromycin. LCMV (Armstrong strain) stocks were plaque purified on Vero cells and grown in BHK-21 cells as described previously (19). For the generation of an acute virus-specific T cell response, mice were inoculated i.p.…”

Section: Methodsmentioning

confidence: 99%

The CD8 Population in CD4-deficient Mice Is Heavily Contaminated with MHC Class II–restricted T Cells

Tyznik

Sun

Bevan

2004

117

107

In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several nominally major histocompatibility complex (MHC) class II–restricted epitopes in addition to the expected responses to MHC class I–restricted epitopes. A similar response by CD8+ T cells to class II–restricted epitopes was not observed in wild-type mice, or in mice that had been acutely depleted of CD4+ T cells just before the immunization. Coincident with this unexpected response to class II–restricted epitopes, it was also observed that the CD8+ response to the class I–restricted epitopes was consistently lower in CD4−/− mice than in wild-type mice. Further experiments suggested that these two observations are linked and that the CD8 population in CD4−/− mice may contain a majority of T cells that were actually selected by recognition of MHC class II molecules in the thymus. These results have implications for understanding CD4 versus CD8 lineage commitment in the thymus, and for the practical use of CD4−/− mice as models of helper deficiency.