In situexpression of B7 and CD40 costimulatory molecules by normal human lung macrophages and epithelioid cells in tuberculoid granulomas

Abstract

SUMMARYNormal alveolar macrophages (AM) are not efficient in inducing the proliferation of resting T lymphocytes, and, rather, tend to inhibit pulmonary immune responses. In contrast, epithelioid cells (EC), activated macrophages that play an essential role in the course of granulomatous responses, appear to stimulate T cell proliferation efficiently. The inability of macrophages to deliver potent costimulatory signals through the B7/CD28 and CD40/CD40L pathways could explain their weak accessory cell activity. Using MoAbs and immunohistochemical techniques, however, we found that essentially all AM in normal human lung tissue expressed B7-1, B7-2 and CD40 molecules, and most of these cells were strongly positive. Pulmonary macrophages in other compartments also expressed these costimulatory molecules; no differences in expression were observed comparing macrophages from smokers and non-smokers. Most AM recovered by bronchoalveolar lavage from normal lung segments also strongly expressed B7-1, B7-2 and CD40 molecules. In comparison, resting blood monocytes were B7-1 ¹ and only moderately positive for B7-2. Activation of monocytes with lipopolysaccharide (LPS) induced expression of these costimulatory molecules to levels similar to that of AM from the control subjects. EC in granulomatous lesions also expressed easily detectable levels of B7-1, B7-2 and CD40. T lymphocytes within and surrounding the granulomas expressed CD28, the counter-receptor for B7, and many of these T cells also expressed B7-1 and B7-2. These findings suggest that both AM and EC can deliver costimulatory signals through B7-1, B7-2 and CD40 molecules, and indicate that the impairment in accessory cell activity observed for normal AM cannot be attributed to the absence of expression of these costimulatory molecules.

Mycobacterium bovis BCG-Induced Granuloma Formation Depends on Gamma Interferon and CD40 Ligand but Does Not Require CD28

“…The cellular composition of granulomas in CD40L Ϫ/Ϫ mice indicated that recruitment of both CD4 ϩ and CD8 ϩ T cells is altered. Although previous immunohistochemical studies have shown that human tuberculoid granulomatous lesions contain readily detectable levels of B7-1 and B7-2 on epithelioid cells and of CD28 on T cells (42), our data indicated that CD28 is dispensable for protective granulomatous responses against BCG in a murine model. T cells from CD28-deficient mice have reduced expression of IL-2 receptor ␣(IL-2R␣), reduced T-helper cell function, and reduced proliferation to concanavalin A but are still able to mount an effective anti-lymphocytic choriomeningitis virus cytolytic immune response in vivo (40).…”

Recombinant interleukin-4-treated macrophages, epithelioid cell surrogates, harbor and arrest Mycobacterium avium multiplication in vitro

“…However, when antigen-pulsed EC surrogates were tested for their ability to prime T lymphocytes in vivo, these cells were more efficient in this function when compared with control macrophages. This result corroborates the assumption that in a granuloma environment ECs may be activating T lymphocytes effectively [19].…”

“…a 0 min ¼ no incubation at 37 C. The presence of costimulatory and adhesion molecules on ECs and/or multinucleated giant cells in granulomas found in infectious [17,19] or autoimmune [18] diseases suggests that antigen presentation takes place in these lesions. Moreover, it has been described that ECs express costimulatory molecules like CD80 (B7-1), CD86 (B7-2) and CD40, which were found in close contact with T lymphocytes in tuberculoid and sarcoid lesions [19]. We have previously shown that EC surrogates express MHC class II [14] and in this report we extended this knowledge, showing that these cells express other molecules involved in antigen presentation such as B7-2, CD40 and CD54 (ICAM-1).…”

Low expression of antigen-presenting and costimulatory molecules by lung cells from tuberculosis patients

“…This is one of the earliest human in vivo results to confirm the prior reports on murine TB (22,37). In one other study of costimulatory molecules in human TB, Soler et al (38) failed to show differences in the expression of CD80/CD86 costimulatory molecules in tubercle granulomas caused by M. tuberculosis. This finding is in apparent contrast to our current findings.…”