Costimulation of purified CD8 ؉ T lymphocytes induces de novo expression of CD4, suggesting a previously unrecognized function for this molecule in the immune response. Here, we report that the CD4 molecule plays a direct role in CD8 ؉ T cell function by modulating expression of IFN-␥ and Fas ligand, two important CD8 ؉ T cell effector molecules. CD4 expression also allows infection of CD8 cells by HIV, which results in down-regulation of the CD4 molecule and impairs the induction of IFN-␥, Fas ligand, and the cytotoxic responses of activated CD8 ؉ T cells. Thus, the CD4 molecule plays a direct role in CD8 T cell function, and infection of these cells by HIV provides an additional reservoir for the virus and also may contribute to the immunodeficiency seen in HIV disease. C D8 ϩ cytotoxic T lymphocytes (CTL) have a major role in antiviral immunity, directly killing virally infected cells and producing antiviral cytokines. Activation of these cells requires interaction of the T cell receptor complex with antigenic peptide and major histocompatibility complex (MHC) class I molecules on antigen-presenting cells (APCs) followed by a second costimulatory signal (1). After activation, there is a coordinated expression of various cell surface molecules, many of which play a direct role in cytotoxic activity. We and others have shown that costimulation of CD8 ϩ T cells from the peripheral blood results in the de novo expression of CD4, a molecule previously thought to be absent on this cell type at this stage of development (2-5). These CD8 ϩ CD4 ϩ cells express higher levels of activation molecules than do costimulated CD8 ϩ T cells lacking CD4 expression (2, 6). CD8 ϩ CD4 ϩ T cells constitute Ϸ3-5% of the human peripheral blood lymphocyte pool (7-10). Certain conditions seem to influence CD8 ϩ CD4 ϩ cell levels in humans, including infection with HIV (11), human T lymphotrophic virus-1 (12), Epstein-Barr virus (8), human herpesvirus 6 (13), and aging (10). CD8 ϩ CD4 ϩ cells also have been observed in monkeys (14-17), and in mice, rats, swine, and chickens (reviewed in ref. 18). In mice, CD8 ϩ CD4 ϩ cell levels increased after inoculation with reovirus or recombinant adenovirus (19,20). In each species, the CD8 ϩ CD4 ϩ populations usually displayed the phenotype of activated or previously activated T cells and, in the studies that assessed the composition of the CD8 dimer, were predominantly CD8␣␤ (versus CD8␣␣) cells (11,15,19). The presence of CD8 ϩ CD4 ϩ cells in normal individuals and the increased representation of these cells in individuals with disease or increased antigenic stimulation suggest a role for this cell type in immunity.The CD4 molecule has an important role in CD4 ϩ T helper (Th) cell development and response to antigen, including functioning as an adhesion molecule, regulating cellular activation and gene expression, and serving as a chemotactic receptor (21-23). Its role as the primary receptor for HIV is well known (24,25). The cytoplasmic tail of the CD4 molecule on Th cells is associated with t...

CD8 ؉ T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8 ؉ T cells induces de novo expression of the CD4 molecule and that ligation of CD4 on this cell type modulates CD8 ؉ T cell activity in vitro. Herein, we investigate how the CD4 molecule expressed on murine CD8 ؉ T cells contributes to CD8 ؉ cell responses in vivo by employing adoptive transfer of CD8 cells from CD4 knockout mice into severe combined immunodeficient (SCID) recipients. Transfer of these cells into syngeneic SCID mice resulted in a decreased immune response to infection by lymphocytic choriomeningitis virus. These decreased responses occurred even in the presence of CD4 ؉ T cells, indicating that this was truly a CD8-cell defect. Similarly, transfer of CD8 ؉ T cells incapable of expressing CD4 into allogeneic SCID mice resulted in a decreased response to alloantigens compared with that of normal CD8 ؉ T cells. Therefore, CD4 expression on CD8 T lymphocytes modulates cytotoxic T lymphocyte function and is critical in vivo for optimal cell-mediated immunity to viral and alloantigens.antiviral response ͉ CD8 ϩ T cells ͉ alloantigen response ͉ cytotoxic T lymphocytes T cell development in the thymus is characterized by the appearance and disappearance of cell-surface CD4 and CD8, which are classic markers of ontogeny. It was previously thought that after synchronous expression of CD4 and CD8, the developing thymocyte becomes CD4 or CD8 single positive, permanently turning off expression of one of these molecules. These single-positive cells are then exported to the periphery to perform their respective functions: CD4 ϩ cells serving primarily as T helper (Th) cells, and CD8 ϩ cells serving primarily as cytotoxic T lymphocytes (CTLs). Our current investigation focuses on the CD8 ϩ T cell population. CD8 ϩ T cells become activated to perform their function when they encounter a specific antigen presented in the context of MHC class I and are costimulated by one of many molecules present on antigen-presenting cells (APCs) (1). A well described series of events is triggered after activation of CD8 ϩ T cells, primarily resulting in CTLs that kill antigen-expressing target cells.In contrast to the notion that commitment to the CD4 or CD8 lineage is complete or permanent after thymopoiesis, extrathymic CD8 ϩ CD4 ϩ cells have been identified in many organisms, including humans, monkeys, mice, rats, swine, and chickens (reviewed in ref.2). Various disease conditions appear to affect the levels of CD8 ϩ CD4 ϩ T cells. In humans, infection with HIV, human T cell leukemia virus, Epstein-Barr virus, human herpesvirus 6, and increasing age have been linked with increased percentages of CD8 ϩ CD4 ϩ T cells in the peripheral blood (3-6). In mice, increases in the CD8 ϩ CD4 ϩ population have been observed after inoculation with reovirus (7), or recombinant adenovirus (8). In most cases, the rise in the percentage of CD8 ϩ CD4 ϩ cells appears to be a dir...

Adjuvant-induced penetration of horseradish peroxidase (HRP) into seminiferous epithelium was studied as a model of adjuvant-induced entry of other proteins, e.g., immunoglobulins. HRP intravenously injected 20 minutes prior to sacrifice (by peraortic perfusion with Karnovsky's fixative) into male guinea pigs that had received Freund's complete adjuvant (FCA) f saline or FCA + testicular homogenate (TH) intradermally seven days previously, entered the peritubular spaces of a moderate number of seminiferous tubules. In those tubules HRP became uniformly distributed in the cytoplasmic matrices (but very rarely in membrane-bound vesicles) of some of the Sertoli cells and presumptive type B spermatogonia. By contrast, HRP injected into normal animals, into animals that had received FCA 4-saline or FCA + TH 3 or 14 days previously or into animals that had received Freund's incomplete adjuvant + saline 3, 7, or 14 days previously gained entry into only occasional peritubular spaces but was never found in any cells of the seminiferous epithelium.These findings are discussed in conjunction with previous findings on immune aspermatogenesis. Hypotheses concerning the intratesticular mechanisms of production of both active and passive immune aspermatogenesis as activated by FCA and the mechanisms whereby FCA may enable or potentiate production of immune globulins are proposed and discussed.

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We have demonstrated that varying degrees of seminiferous epithelial damage up to and including aspermatogenesis could be induced by transfer of immune serum. Aspermatogenesis was consistently produced when the recipient guinea pigs were pretreated with Freund’s complete adjuvant plus saline intradermally 7 days prior to transfer of serum from donor guinea pigs immunized 7 days previously with testicular homogenate in Freund’s complete adjuvant. Aspermatogenesis was also induced by transfer of cells of lymph node, spleen or peritoneal exudate from the same immune donor animals.

Abdominal ultrasonograms of recumbent, supine adult subjects were used to measure the angle formed between the horizontal plane and a plane along the anterior border of upper lumbar vertebral bodies. The angle, referred to as phi, for male and female subjects averaged 8.8 degrees. When this angle was compared in subjects with the hips flexed and extended, there was no significant difference. There was a significant difference between subjects in a recumbent position and a standing position. The amount of angulation was compared to the age of the individual and found to have a low correlation coefficient. The angle phi appears to be a good indicator of the amount of lordosis, it related well to previous methods of measuring lordosis, and it is a benign procedure in a genetically sensitive region.

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