In vitro exposure to highly cytopathic HIV-1 X4 strains increases expression of mucosa-associated integrins on CD4(+) T cells.

To determine whether infection with HIV-1 strains of different tropisms would influence expression of the mucosa-associated integrins alpha 4 beta 7 and alpha E beta 7 or the lymph node homing receptor L-selectin on peripheral T lymphocytes, cells were infected with the CXCR4-tropic (X4)/syncytium-inducing (SI) HIV-1(IIIB) strain or with X4/SI or CCR5-tropic (R5)/non-SI (NSI) primary human isolates. Flow cytometric analyses of CD4(+) T cells from cultures infected with HIV-1(IIIB) and one X4/SI primary HIV-1 isolate revealed a significant increase in surface expression of alpha 4 beta 7 and alpha E beta 7 12 days after infection. L-selectin expression was not significantly affected on CD4(+) T cells. However, infection with another X4/SI and two R5/NSI primary HIV-1 isolates did not significantly alter homing receptor expression on CD4(+) T cells. Since a higher degree of CD4 cytopathicity occurred in those cultures having increased integrin expression, these data suggest that significantly altered mucosal homing receptor expression on CD4(+) T cells may result as a "bystander" effect after infection with some cytopathic isolates of HIV-1.

Human and nonhuman primate lymphocytes engrafted into SCID mice reside in unique mesenteric lymphoid structures.

The present study compares the location and phenotype of B lineage lymphocytes in tissues from SCID mice engrafted with PBMC of human, chimpanzee, and pig-tailed macaque origin. In mice repopulated with both human and nonhuman primate lymphocytes, plasma cells were found in the peritoneal cavity in vascularized structures located in the mesentery near the pancreas, intestines, and spleen. The predominant isotype of the plasma cells was IgG; IgM and IgA cells were also present. Kappa and lambda light chains were expressed by 62% and 38% of the Ig-containing cells, respectively. J chain expression occurred in most cells irrespective of the Ig isotype. In the SCID mice engrafted with human lymphocytes, a few IgM-containing cells were found in the spleen; plasma cells were not found in other tissues, including the intestine. The aggregation of plasma cells did not appear to be a result of infection with EBV. T cells were rarely found in the lymphoid aggregates but were recovered from the spleen and peritoneal lavage. Human Ig levels in the serum of engrafted mice reflected the isotype distribution of the cells with IgG > IgM > or = IgA.

HIV-1/simian immunodeficiency virus infection of human and nonhuman primate lymphocytes results in the migration of CD2+ T cells into the intestine of engrafted SCID mice.

Increased lymphocytic infiltration of intestinal tissues has been observed in patients infected with HIV-1 and in SIV-infected rhesus macaques. To determine whether HIV-1 and SIV infections influence the homing of human and nonhuman primate PBMC to intestinal tissues, we engrafted SCID mice with human or nonhuman primate PBMC and infected them with either cell-free or cell-associated HIV-1 or SIV. In mice that received both PBMC and virus, human or nonhuman primate CD2+ T cells were found in intestinal tissues, primarily in the intraepithelial lymphocyte compartment and lamina propria. Immunomagnetic sorting revealed that these cells were derived from the CD4+ population. Using gag-specific primers, PCR analysis of these tissues detected the presence of HIV-1 proviral DNA. However, in SCID mice that were engrafted with either human or nonhuman primate PBMC and no HIV-1 or SIV, CD2+ T cells were not detected in intestinal tissues. These results indicate that HIV-1 and SIV can modulate the migratory properties of human and nonhuman primate T cells in the SCID mouse model.

Human peritoneal B-1 cells and the influence of continuous ambulatory peritoneal dialysis on peritoneal and peripheral blood mononuclear cell (PBMC) composition and immunoglobulin levels.

In mice, peritoneal B cells are composed of a unique B-1 cell population which can repopulate the intestinal lamina propria with IgA-producing cells, as well as contribute to the majority of serum IgM. In this study, peritoneal lymphocytes from patients starting continuous ambulatory peritoneal dialysis (CAPD) and from women undergoing bilateral tubal ligation (BTL) were analysed for the presence of a B-1 cell population as well as the expression of potential homing receptors. Up to 63% of the peritoneal B cells express surface antigen CD5, and most peritoneal lymphocytes express the mucosal homing receptors, alpha4 beta7 and alphaE beta7. When analysing serial samples collected from patients from the beginning of dialysis to 1 year, no marked changes were observed in serum or salivary immunoglobulin levels, although the peritoneal lymphocyte population was reduced by 50%. These data suggest that the phenotype of human peritoneal B-1 cells is similar to that of mice, but the contributions to the immune system may differ.