CD8+ T-cell effector molecules are differentially expressed in blood and gastrointestinal mucosa in chronic HIV-1 infection

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.172-172.14
• Main Authors: Shacklett, Barbara L., Kiniry, Brenna E., Somsouk, Ma, Hunt, Peter W., Deeks, Steven G.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.172.14

CD8+ T-cells in human gastrointestinal mucosa exhibit reduced perforin expression and weak cytotoxicity compared to their counterparts in blood. We previously reported that these cells are predominantly T-bet-low and Eomesodermin-negative. Nevertheless, in response to antigenic stimulation these cells degranulate and express cytokines and chemokines. The goal of this study was to elucidate expression patterns of granzymes (Gzm) A, B and K in conjunction with perforin in rectosigmoid CD8+ T-cells during chronic HIV-1 infection and determine whether these patterns vary with disease status. We used flow cytometry to compare intracellular Gzm A, B, K and perforin in resting CD8+ T-cells from blood and rectosigmoid biopsies of HIV-1+ controllers; viremic individuals; virologically suppressed individuals on antiretroviral therapy; and seronegatives. Expression of perforin and GzmB, but not GzmA or GzmK, was reduced in mucosa compared to blood. A large fraction of rectosigmoid CD8+ T-cells did not express granzymes or were single-positive for GzmA. Rectosigmoid CD8+ T-cells appeared skewed towards cytokine production rather than cytotoxicity, with cells expressing multiple cytokines/chemokines lacking perforin and granzyme expression. Percentages of mucosal CD8+ T-cells expressing cytotoxic effectors were higher in HIV-1+ groups, compared to seronegatives. These data support the interpretation that perforin and granzymes are differentially regulated, and display distinct expression patterns in blood and rectosigmoid T-cells. These findings also reinforce our previous work, suggesting that rectosigmoid CD8+ T-cells are programmed for cytokine polyfunctionality rather than cytotoxicity.