CD4+T cells require either B cells or CD8+T cells to control spread and pathogenesis of a neurotropic infection.
Immunity within the brain, specifically to virus-infected neurons, must be controlled to prevent neuron loss and impairment, though the process by which this occurs remains unclear. Here, we use a mouse model of neuron-restricted measles virus infection, in which immunocompetent adults survive challenge, whereas T and B cell-deficient mice succumb. This model allowed us to more precisely define the contributions of CD4+T cells, CD8+T cells, and B cells in neuroprotection. Both B cell knockout mice and mice depleted of CD8+T cells survive challenge and show no signs of illness, though are less able to control viral replication than immunocompetent mice. In contrast, depletion of CD4+T cells results in disease and death in all infected mice, though the kinetics of illness are delayed compared to RAG knockout mice. Our data suggest a coordinated interplay of adaptive immune components, which collectively controls viral spread and limits neuropathogenesis.
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States; Drexel University College of Medicine, Department of Microbiology and Immunology, 2900 W. Queen Lane, Philadelphia, PA 19129, United States.
Andreas C
AC
Solomos
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States.
Kevin J
KJ
O'Regan
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States. Electronic address: glenn.rall@fccc.edu.
Glenn F
GF
Rall
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008457:Measles / Q000276:immunology* / Q000821:virology; D008459:Measles virus / Q000472:pathogenicity* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D056189:Viral Tropism; D014774:Virulence
Adaptive immunity; Measles; Neuron; Transgenic mice
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