FcγR-mediated Functions Research Articles

Innate and Adaptive Anti-SIV Responses in Macaque Semen: Implications for Infectivity and Risk of Transmission.

HIV-1 infection is transmitted primarily by sexual exposure, with semen being the principal contaminated fluid. However, HIV-specific immune response in semen has been understudied. We investigated specific parameters of the innate, cellular, and humoral immune response that may affect semen infectivity in macaques infected with SIVmac251. Serial semen levels of cytokines and chemokines, SIV-specific antibodies, neutralization, and FcγR-mediated functions and SIV-specific T-cell responses were assessed and compared to systemic responses across 53 cynomolgus macaques. SIV infection induced an overall inflammatory state in the semen. Several pro-inflammatory molecules correlated with SIV virus levels. Effector CD8+ T cells were expanded in semen upon infection. SIV-specific CD8+ T-cells that expressed multiple effector molecules (IFN-γ+MIP-1β+TNF+/−) were induced in the semen of a subset of SIV-infected macaques, but this did not correlate with local viral control. SIV-specific IgG, commonly capable of engaging the FcγRIIIa receptor, was detected in most semen samples although this positively correlated with seminal viral load. Several inflammatory immune responses in semen develop in the context of higher levels of SIV seminal plasma viremia. These inflammatory immune responses could play a role in viral transmission and should be considered in the development of preventive and prophylactic vaccines.

Nonspecific immunity in pregnancy: monocyte surface Fc γ receptor expression and function

The state of pregnancy is an immunological enigma during which the body must prevent rejection of the antigenically foreign fetus while at the same time maintain sufficient maternal host defense mechanisms to combat infection. Although most studies on the immunology of pregnancy focus on immune suppression, several studies have shown an increase in nonspecific host defense, which is postulated to be a compensatory mechanism for decreased specific immunity during pregnancy. Studies in this laboratory have shown that monocyte surface Fc γRI (CD64) and Fc γRII (CD32) expression progressively increase throughout pregnancy, while surface MHC class II expression remains unchanged. Functional studies revealed that the number of phagocytic monocytes which could be isolated from pregnant women was increased. These cells exhibited an increased capacity to ingest IgG-opsonized human erythrocytes. This study shows for the first time that monocyte surface Fc γR expression and Fc γR-mediated functions are increased during pregnancy. These results support the hypothesis that nonspecific immunity as represented by Fc γR expression and function is increased during pregnancy.

Cyclophosphamide augments ADCC by increasing the expression of Fc-receptors

Previous reports demonstrated that cyclophosphamide (Cy) enhances two Fcγ receptor (FcγR) mediated functions: antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. In this paper we examine the mechanisms whereby Cy modifies the cytotoxic capacity of mouse splenocytes. The results indicate that the observed augmentation of ADCC could not be attributed to a higher proportion of macrophages and/or polymorphonuclear leukocytes (PMN), but rather to an enhanced activity per effector cell. Binding studies showed that this augmentation was associated with an increased number, but not an increased avidity of FcγR sites. The possibility that the enhanced FcγR expression by Cy may result in the alteration of other FcγR-mediated functions is discussed.