CD4+ T cells but Not CD8+ or gammadelta+ lymphocytes are required for host protection against Mycobacterium avium infection and dissemination through the intestinal route.

TitleCD4+ T cells but Not CD8+ or gammadelta+ lymphocytes are required for host protection against Mycobacterium avium infection and dissemination through the intestinal route.
Publication TypeJournal Article
Year of Publication2005
AuthorsPetrofsky M, Bermudez LE
JournalInfection and immunity
Volume73
Issue5
Pagination2621-7
Date Published2005 May
ISSN0019-9567
KeywordsAdministration, Oral, Animals, Antigens, CD18, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, Humans, Intestines, Liver, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium avium Complex, Mycobacterium avium-intracellulare Infection, Receptors, Antigen, T-Cell, gamma-delta, Spleen
Abstract

Disseminated Mycobacterium avium infection is common in AIDS patients that do not receive anti-AIDS therapy and in patients for whom therapy fails. M. avium is commonly acquired by ingestion, and a large number of AIDS patients have M. avium in their intestinal tracts. To better understand the dynamics of the infection in patients with AIDS, we studied orally infected mice. To determine if immunocompetent mice challenged orally with M. avium can develop protection against the infection, and if so, which cell population(s) is responsible for the protection, we exposed wild-type as well as CD4(-/-), CD8(-/-), and gammadelta(-/-) knockout mice to low concentrations of M. avium strain 101 given orally, followed by treatment with azithromycin. After 1 month, the mice were challenged with kanamycin-resistant M. avium 104. Only CD4(+) T cells appeared to be required for protection against the second challenge. Both CD4(+) and CD8(+) T cells produced comparable amounts of gamma interferon after the first exposure to the bacterium. Tumor necrosis factor alpha was elevated in CD4(+) T cells but not in CD8(+) T cells. Following exposure to a small inoculum of mycobacteria orally, wild-type mice did not develop disseminated infection for approximately 4 months, although viable bacteria could be observed in the mesenteric lymph nodes. The ingestion of small numbers of M. avium cells induces a protective immune response in the intestines against subsequent infection. However, the bacteria remain viable in intestinal lymph nodes and might disseminate later.

Alternate JournalInfect. Immun.