Faculty Collaboration Database

Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa. J Immunol 1999 Jan 01;162(1):540-9

Date

01/14/1999

Pubmed ID

9886431

Scopus ID

2-s2.0-0032931931 (requires institutional sign-in at Scopus site)   88 Citations

Abstract

The identification of mucosal immune responses required for protection against sexual transmission of HIV is essential for the development of an efficacious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) of 11 rhesus monkeys following colonic exposure to two molecular clones of SIV. Two monkeys had no signs of infection. Three monkeys became persistently infected. Transient infections, characterized by the sporadic detection of virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the monkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP. Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP. Three or six months postexposure, these animals and four naive controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670. All four monkeys with strong SIV env-specific MHC-restricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protected. These experiments provide the first direct evidence that transient mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. Furthermore, a strong correlation between SIV env-specific MHC-restricted CTL in the LP and protection against colonic mucosal challenge was observed.

Author List

Murphey-Corb M, Wilson LA, Trichel AM, Roberts DE, Xu K, Ohkawa S, Woodson B, Bohm R, Blanchard J

Author

B Tucker Woodson MD Chief, Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Colon
Cytotoxicity, Immunologic
Dose-Response Relationship, Immunologic
Female
Gene Products, env
Gene Products, gag
Histocompatibility Antigens Class I
Intestinal Mucosa
Jejunum
Lymphocyte Activation
Macaca mulatta
Male
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
T-Lymphocytes, Cytotoxic