Induction of Mucosal Homing Virus-Specific CD8⁺T Lymphocytes by Attenuated Simian Immunodeficiency Virus

Abstract

Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8 ؉ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor ␣4␤7 and traffic to the intestinal mucosa. SIV-specific CD8 ؉ T cells expressing ␣4␤7 were detected in peripheral blood and intestine of macaques infected with attenuated SIV. In contrast, virusspecific T cells in blood of animals immunized cutaneously by a combined DNA-modified vaccinia virus Ankara regimen did not express ␣4␤7. These results demonstrate the selective induction of SIV-specific CD8 ؉ T lymphocytes expressing ␣4␤7 by a vaccine approach that replicates in mucosal tissue and suggest that induction of virus-specific lymphocytes that are able to home to mucosal sites may be an important characteristic of a successful AIDS vaccine.

Hyperattenuated Recombinant Influenza A Virus Nonstructural-Protein-Encoding Vectors Induce Human Immunodeficiency Virus Type 1 Nef-Specific Systemic and Mucosal Immune Responses in Mice

“…The migratory behavior of immune cells as postulated by the concept of the common mucosal immune system has been most frequently documented for mucosal B cells but only rarely for activated mucosal T cells (36). However, the selective induction and homing of antigen-specific CD8 ϩ T lymphocytes expressing ␣4␤7 adhesion molecules derived from the blood circulation upon mucosal immunization with attenuated simian immunodeficiency virus was reported recently (8). I.n.…”

Home sweet home: how do virus specific T cells navigate to the skin?

“…There is a marked gradation in the nature of this epithelium, from the moist noncornified vaginal mucosa, which is bathed in antibodies and immune cells, to the dry, fully cornified vulval epithelium. Do the homing receptors on CD8 cells differ for these two sites, as has been suggested by studies with attenuated Simian immunodeficiency virus vaccine candidates (12)? It may be significant in this regard that CLA expression differs among CD8 lymphocytes specific for EBV, CMV, and HSV, viruses that are shed from adjacent sites in the orolabial and cervico-vaginal epithelia.…”

GUCY2C-targeted cancer immunotherapy: past, present and future

“…The ideal target would be universally expressed by cancer, induce robust immune responses against tumors, but have a low risk of autoimmunity. Previous observations of immune system compartmentalization suggested that this could be achieved by targeting mucosa-specific differentiation antigens [16][17][18][19][20][21][22][23][24][25][26][27]. Indeed, the adaptive immune system is comprised of specialized compartments that serve distinct, but overlapping, functions, that often contain unique cell populations and that frequently do not communicate with one another.…”