Role of the indigenous microbiota in maintaining the virus-specific CD8 memory T cells in the lung of mice infected with murine cytomegalovirus.
The potent role of indigenous microbiota in maintaining murine CMV (MCMV)-specific memory T cells, which were measured by multimer staining, was investigated using germfree (GF) mice. When the BALB/c mice bred under specific pathogen-free (SPF) conditions were i.p. infected with 0.2 LD(50) of MCMV, high frequencies of CD69(+)/CD44(+) MCMV-specific CD8 T cells were noted in the lungs even at 6-12 mo after infection (11.1 +/- 3.2 and 9.8 +/- 0.9%, respectively). In contrast, even though the viral load and expression levels of mRNA of such cytokines as IL-2, IL-7, IL-15, and IFN-gamma in the lungs of MCMV-infected GF mice were comparable to those of infected SPF mice, the frequencies of MCMV-specific CD8 T cells in the lungs of infected GF mice were kept lower than 1% at 6-12 mo after infection. In addition, the reconstitution of microbiota of MCMV-infected GF mice by orally administering a fecal suspension prepared from SPF mice restored the frequencies of both CD8(+)/multimer(+) and CD8(+)/multimer(-) T cells to levels similar to those found in SPF mice. These results suggested the indigenous microbiota to play a crucial role in the expansion and maintenance of viral-specific CD8 memory T cells, probably by cross-reactivity between the antigenic epitope of the MCMV-specific memory T cells and the variety of peptides derived from the members of the microbiota. Such cross-reactivity may thus be a major feature of those cells.
Tanaka
Kazuo
K
Laboratory of Infectious Diseases, Tokai University School of Medicine, Isehara, Kanagawa, Japan. tanakaka@is.icc.u-tokai.ac.jp
Sawamura
Sadaaki
S
Satoh
Tadayuki
T
Kobayashi
Kiyoshi
K
Noda
Satoshi
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007422:Intestines / Q000382:microbiology*; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus; D013047:Specific Pathogen-Free Organisms
D016207:Cytokines; D007371:Interferon-gamma