Cervicovaginal lamina propria lymphocytes: Phenotypic characterization andtheir importance in cytotoxic T-lymphocyte responses to simian immunodeficiency virus SIVmac251

Most human immunodeficiency virus (HIV) type I infections occur by the muco sal route. Thus, it is important to assess the immune responses to HIV in t he vaginal, cervical, and rectal compartments. Here we quantitated the viru s-specific CD8(+) T-cell response and characterized the phenotype of lympho cytes in the genital tracts of naive macaques, macaques acutely or chronica lly infected with simian immunodeficiency virus SIVmac251, and macaques chr onically infected with chimeric simian/human immunodeficiency virus SHIVKU2 . Vaginal biopsy samples or samples obtained at the time of euthanasia were used in this analysis. The percentage of Gag-specific, tetramer-positive T cells was as high as 13 to 14% of the CD3(+) CD8(+) T-cell population in t he vaginal and cervical laminae propriae of both SIVmac251 and SHIVKU2 chro nically infected macaques. In most cases, the frequency of this response in the cervicovaginal compartment far exceeded the frequency in the blood or the draining iliac lymph node. Vaginal laminae propriae of naive macaques c ontained 55 to 65% CD3(+) CD8(+) cells and 28 to 34% CD3(+) CD4(+) cells, w hile the majority of intraepithelial cells were CD8(+) T cells (75 to 85%). For the same cells, the surface expression of CD62L was low whereas that o f alphaE beta7 was high. No difference in the expression of CD45RA on CD8() T cells was observed in the chronic stage of SIVmac251 infection. Althoug h no decrease in the percentage of CD4(+) cells in the genital tract was ob served within the first 12 days of infection, by 6 weeks from SIVmac251 inf ection and thereafter the percentage of CD4(+) T cells was decreased in the laminae propriae of the vagina and cervix. Expression of CD45RA did not di ffer in naive and acutely SIVmac251 infected macaques. Information on the q uality and quantity of local immune responses may help in the design of vac cine strategies aimed at containing viral replication at the site of viral encounter.