HLA expression in hemopoietic development. Class I and II antigens are induced in the definitive erythroid lineage and differentially modulated by fetal liver cytokines.

We investigated the expression of HLA Ag on hemopoietic progenitors (burst-forming unit E, CFU-E, and CFU-granulocyte-macrophage) and precursors from human embryonic fetal liver (FL) and peripheral blood at 5 to 9 wk postconception. The expression on progenitors was evaluated by complement-mediated cytotoxicity followed by assay of residual progenitors in clonogenic culture; immunofluorescence and RIA were used for differentiated precursors. HLA Class I and II Ag are not expressed on the primitive erythroid lineage, i.e., on yolk sac-derived megaloblasts circulating in 5- to 6-wk peripheral blood. However, they are gradually induced on the definitive erythroid lineage in FL. Their expression on progenitors is first detected at 6 wk and shows a progressive increase through 9 wk, up to greater than or equal to 50% of adult values. A similar expression pattern is observed for FL erythroblasts. Incubation of 6-wk FL erythroid cells with IFN-alpha, -beta, or -gamma, or TNF-alpha induces a sharp rise of the expression of HLA class I, but not HLA class II Ag on both progenitors and precursors. In contrast, incubation with PHA-stimulated adult leukocyte-conditioned medium causes a marked increase of both HLA-ABC and HLA class II Ag expression. We hence investigated the effect of cytokines present in leukocyte-conditioned medium on the expression of HLA class II Ag: although IL-1 alpha, IL-2, and granulocyte-macrophage-CSF do not exert a significant action, IL-1 beta and IL-4 induce a marked increase of HLA class II, but not class I, Ag expression on 6-wk FL progenitors and precursors. Low amounts of IFN-gamma, TNF-alpha, and IL-1 beta were detected in the supernatants and extracts of 6-wk FL cells. The concentrations of these cytokines in both supernatants and extracts sharply increase in the 7- to 8-wk period, particularly for TNF-alpha and IL-1 beta, thus indicating a direct correlation with the rise of HLA Ag expression on FL erythroid cells in the same period. In conclusion, the expression of HLA class I and II Ag is not detected on primitive megaloblasts, but is gradually induced on definitive FL progenitors and precursors, possibly via production of specific cytokines in the FL microenvironment, i.e., IFN-gamma and TNF-alpha for class I Ag and IL-1 beta for class II Ag.     

Peripheral blood T-lymphocytes of patients with chronic B-cell lympholeukemia express Ia-like antigens

15.7 +/- 3.5% of sheep rosette-forming cells (SRFC) were isolated from the peripheral blood of 11 patients with B-cell chronic lympholeukemia (B-CLL). SRFC did not express surface immunoglobulins, antigens of nondifferentiated blasts and antigens of early T-cell precursors, while NK-cell antigen expression was low. 6 of 11 patients revealed 44.6 +/- 19.6% of Ia-like antigens in SRFC. Ia-like antigen expression was 4.8 +/- 0.6% in SRFC isolated from the peripheral blood of 19 healthy donors. The expression of Ia-like antigens in T cells of patients with B-CLL is suggested to be related to the activation of regulatory T-lymphocyte subpopulation.     

Cell lineage segregation during bursa of Fabricius ontogeny

The population dynamics of myeloid and lymphoid lineages during bursa of Fabricius ontogeny were analyzed by immunofluorescence by using two monoclonal antibodies (mAb). CL-1 mAb reacts with all chicken hemopoietic cells, except mature erythrocytes. L22 mAb reacts with bursa and bursa-derived lymphocytes, with a minor subset of macrophages and with some cells of the thymic medulla. The staining of embryonic bursas by these antibodies helps to distinguish between two different lineages of hemopoietic cells: CL-1+/L22+ cells represent B lymphocytes and a minor subset of macrophages, while CL-1+/L22- cells correspond to most of the macrophages and to the granulocytes, which disappear at the end of the embryonic life. CL-1+/L22- as well as CL-1+/L22+ cells were first observed outside the bursal rudiment. This indicates that there is a pre-bursal segregation between these two hemopoietic lineages and that two different kinds of precursors colonize the bursal rudiment at about the same time (day 9 for CL-1+/L22- cells and days 9 or 10 for CL-1+/L22+ cells). Moreover our data show that the colonization of the bursal epithelium by hemopoietic precursors is a two-step phenomenon. The first cells which enter belong to the CL-1+/L22- lineage, express Ia-like antigens at a high level, are dendritic in morphology, and represent cells of the macrophage/dendritic cell lineage. They are responsible for the formation of the epithelial bud which are then colonized by a small number of lymphoid precursors which belong to the CL-1+/L22+ lineage. Quail-chick bursa grafting experiments were also performed and the grafts were examined for CL-1 (restricted to chicken hemopoietic cells) and L22 reactivity. These observations confirmed our previous findings about the kinetics of the colonization of bursal rudiment by hemopoietic precursors and give support for a pre-bursal segregation between two hemopoietic pathways.     

Identification of cell surface antigens present on murine hematopoietic stem cells

Nine antigens found on murine bone marrow cells were examined to define their pattern of expression in murine hematopoietic differentiation. Lymphocyte function antigen (LFA-1), heat stable antigen (recognized by M1/69), common leukocyte antigen (CLA, T200, Ly-5) and Lgp100a (recognized by 30-C7) were present on early hematopoietic progenitors, BFU-E, CFU-E, CFU-GM, and CFU-M. All antigens found on progenitors were found on some immature precursor cells, myeloblasts, erythroblasts, or monoblasts, but their pattern of expression on identifiable hematopoietic cells varied. Three of these antigens, LFA-1, heat stable antigen recognized by M1/69, and CLA, were expressed on leukocytes of all stages of maturity but were lost from the erythroid lineage during differentiation. MAC-1, Forssman antigen, heat stable antigen (recognized by M1/75), anti-P-95 (recognized by M5/113), and Ia (recognized by M5/114) were found only on differentiated hematopoietic precursors or mature cells. The expression of these antigens was more lineage-specific. MAC-1 and heat stable antigen (recognized by M1/75) were restricted to either mature myeloid or erythroid cells, respectively. The marked differences in distribution of these antigens suggest that they may be useful in negative or positive selection experiments to enrich progenitors, and that some of them may have a functional role in differentiation.     

Alteration of vimentin intermediate filament expression during differentiation of human hemopoietic cells

We describe the alterations of vimentin intermediate filament (IF) expression in human hemopoietic committed precursors as they differentiate into mature cells of the erythroid, granulomonocytic, megacaryocytic and lymphoid lineages. A double labelling fluorescence procedure was used to identify hemopoietic cells expressing lineage-specific antigens and to decorate the vimentin IF network. Whereas very early progenitors from each lineage expressed vimentin, the density and organization of the network differed strikingly as the cells matured on a given pathway. T lymphocytes, monocytes and granulocytes retained vimentin expression at all stages of maturation. In contrast, megakaryoblasts lose vimentin expression at a very early stage of differentiation, erythroblasts at variable steps between the committed erythroid cell and the red cell. Finally, B lymphocytes tend to lose vimentin expression later when they mature into plasma cells.     

Recombinant murine IL-3 fails to stimulate T or B lymphopoiesis in vivo, but enhances immune responses to T cell-dependent antigens

We have explored the in vivo effect of IL-3 on the lymphopoiesis and humoral responses of mice bearing osmotic minipumps loaded with murine rIL-3 for 1 to 4 wk. A marked splenomegaly due to the accumulation of hemopoietic precursors was seen, but no increase was found in the lymphoid organs in the total number of cells belonging to the T or B lymphocyte lineage, i.e., of L3T4+ or Lyt-2+, or of allospecific cytotoxic T lymphocyte precursor for the T lineage, or of sIg+ or B220+ cells, or of B colony-forming cells for the B lineage; total activity of natural killer and lymphokine-activated killer cells was decreased. In contrast to the splenomegaly, a marked diminution in the number of thymocytes was observed, suggesting that rIL-3 in large amounts does suppress the T lymphopoiesis, perhaps as the result of the selective stimulation of early progenitor cells toward the hemopoietic pathway. rIL-3 perfusion during immunization increased the IgM and IgG responses to a T cell-dependent antigen, human IgG, and prevented tolerance induction by the deaggregated human IgG, although in the same conditions it did not modify the response to a T cell-independent antigen. Our results suggest that in vivo IL-3 does not act directly on lymphocytes or their precursors, but may potentiate the humoral immune response to T cell-dependent antigens, presumably by acting on accessory cells.     

Analysis of human bone marrow with monoclonal antibodies

In order to study the antigenic phenotype of different hemopoietic cells, we used a series of monoclonal antibodies to investigate normal bone marrow in a standard immunofluorescence assay. The antibodies detected the following antigens: HLA-ABC, beta 2-microglobulin (beta 2m), HLA-DR (Ia), a lymphocyte subset and specific antigen (T and B) HuLy-m2, m3, T lymphocyte antigen (HuLy-m1), lymphocyte T200 antigen (HuLy-m4), a viral-associated antigen (HuLy-m5), and platelet-specific glycoproteins IIb-IIIa (HuPl-m1). The following results were obtained: (a) normoblasts were weakly HLA-ABC+, beta 2m+ and Ia-; all other lymphocyte and platelet antigens were not detected. (b) Myeloid cells at all stages of differentiation (promyelocytes, myelocytes, metamyelocytes, and neutrophils) were HLA-ABC+; beta 2m+; HuLy-m1-, m2-, m3+/- (20%), m4+, m5+/- (20%); HuPl-m1-; in addition, promyelocytes and myelocytes were Ia+ but neutrophils and metamyelocytes were Ia-. (c) Lymphocytes were HLA-ABC+, beta 2m+, Ia+/- (20-30%), HuLy-m1+/- (40-50%), m2+/- (60-70%), m3+, m4+, m5+; Pl-m1-. (d) Platelets and megakaryocytes were HLA-ABC+; beta 2m+; Ia-; HuLy-m1+-, m2-, m3-, m4-, m5-, HuPl-m1+, and the putative "megakaryocyte precursors" were HuPl-m1+, Ia-, HuLy-m1-. The different cell types in bone marrow could readily be distinguished, particularly cells of the myeloid series (Ia and HuLy-m4, m5), lymphocytes (Ia and HuLy-m1, m2, m3), and platelets and their precursor cells (HuPl-m1). This simple method of defining cellular phenotypes in bone marrow has demonstrated the practicality of using monoclonal antibodies to identify marrow cells and should be of diagnostic value.     

HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination

Our knowledge of the mechanisms underlying tumor-specific immune response and tumor escape has considerably increased. HLA class I antigen defects remain an important tumor escape mechanism since they influence the interactions between tumor cells and specific T and NK cells in the course of malignant disease. We have studied here HLA class I expression in six subcutaneous metastases obtained from a melanoma patient immunized with an autologous melanoma cell vaccine (M-VAX). We report in this paper that HLA class I antigen expression on these metastatic lesions strongly correlated with the course of the disease. The three metastases that were partially regressing at the time of their excision showed a strong HLA class I expression, whereas the progressing ones showed a very weak or negative staining with most of the anti-HLA class I mAbs used. Real-time quantitative PCR of the samples obtained from microdissected tumor tissue revealed a significant difference in the mRNA levels of HLA-ABC heavy chain and beta2m between the two types of metastases, i.e., lower levels in progressing metastases and high levels in regressing ones, confirming the immunohistological findings. This is, to our knowledge, the first report where the clinical outcome of different HLA class I positive and negative melanoma metastases can be clearly correlated with the regression and progression of the disease, respectively.     

Minimal contribution of marrow-derived endothelial precursors to tumor vasculature

During embryogenesis, vascular and hemopoietic cells originate from a common precursor, the hemangioblast. Recent evidence suggests the existence of endothelial precursors in adult bone marrow cells, but it is unclear whether those precursors have a role in tumor neovascularization. In this report, we demonstrate that murine bone marrow contains endothelial progenitors, which arise from a cell with self-renewing capacity, and can integrate into tumor microvasculature, albeit at a very low frequency. A transgenic double-reporter strategy allowed us to demonstrate definitively that tumor bone marrow-derived endothelial cells arise by transdifferentiation of marrow progenitors rather than by cell fusion. Single cell transplants showed that a common precursor contributes to both the hemopoietic and endothelial lineages, thus demonstrating the presence of an adult hemangioblast. Furthermore, we demonstrate that increased vascular endothelial growth factor (VEGF)-A secretion by tumor cells, as well as activation of VEGF receptor-2 in bone marrow cells does not alter the mobilization and incorporation of marrow-derived endothelial progenitors into tumor vasculature. Finally, in human umbilical cord blood cells, we show that endothelial precursors make up only approximately 1 in 10(7) mononuclear cells but are highly enriched in the CD133+ cell population. By ruling out cell fusion, we clearly demonstrate the existence of an adult hemangioblast, but the differentiation of marrow stem cells toward the endothelial lineage is an extremely rare event. Furthermore, we show that VEGF-A stimulation of hemopoietic cells does not significantly alter this process.     

Interferon-gamma modulates HLA class II antigen expression on cultured human thymic epithelial cells

Cultures of human thymic epithelial cells (TEC) were tested for the expression of HLA class I (A, B, C) and class II (DR and DC) antigens by indirect immunofluorescence. The epithelial nature of the cells was proven by using an antikeratin antiserum. A high level of expression (close to 100% positive cells) of HLA class I antigens was observed on TEC at the beginning of the culture and remained unchanged for up to 12 days. In contrast, HLA class II antigen expression (85% DR+ and 75% DC+ cells on day 2) decreased gradually and reached very low levels (less than 5% DR+ or DC+) by day 7 of culture. This loss of class II antigen expression was not seen when cultures were performed in the presence of supernatants from activated T cells containing interferon-gamma (IFN-gamma). Furthermore, the presence of recombinant IFN-gamma (rIFN-gamma) in the medium from the onset of culture maintained HLA-DR and DC antigen expression on a high number of cells (comparable to that observed on day 2 of culture). A large percentage of rIFN-gamma-treated cells also showed intracytoplasmic HLA-DR antigen expression. Addition of rIFN-gamma at various times after the onset of the culture led to a reinduction of DR and DC antigen expression. This effect of rIFN-gamma was observed in 48 hr with concentrations as low as 10 IU/ml and was apparently specific for this IFN species, in that rIFN-alpha was unable to modify HLA class II antigen expression at concentrations up to 1000 IU/ml. The increased expression of HLA class II antigen was truly due to induction in individual TEC, rather than selection of class II-positive cells, because induction under the influence of IFN-gamma was reversible and occurred in the absence of proliferation in mitomycin-treated or gamma-irradiated cultures. Our results indicate that synthesis and membrane expression of class II HLA antigens are enhanced by IFN-gamma in TEC cultures. This finding raises the possibility that IFN-gamma participates in the mechanisms that assure the permanent expression of DR and DC antigens observed in TEC in vivo, with potentially important functional consequences in terms of education for self recognition.     

Purification of immunologically functional subsets of human Ia-like antigens on a monoclonal antibody (Q5/13) immunoadsorbent

Serologic and immunochemical asays have shown that the monoclonal antibody Q5/13 recognizes an antigenic determinant expressed on a subset of human Ia-like antigens. Testing with a panel of HLA typed B lymphoid cells has shown that this determinant is different from those defining the serologic polymorphism of HLA-DR antigens. The monoclonal antibody Q5/13 has been used to purify subsets of human Ia-like antigens, which are immunologically functional. These reagents should facilitate the characterization of structural and functional properties of human Ia-like antigens.     

Increased Qa-m7 antigen expression is characteristic of primitive hemopoietic progenitors in regenerating marrow

Developmentally early murine hemopoietic progenitor cells of high proliferative potential (HPP-CFC), which are detectable in clonal agar culture in the presence of the lineage-specific hemopoietic growth factor, colony-stimulating factor-1 (CSF-1) plus hemopoietin-1 (H-1), or interleukin 3 (IL 3), express relatively high levels of the Qa-m7 antigenic determinant. This determinant is progressively lost during differentiation, and the more committed progenitors which grow in the presence of CSF-1 alone are essentially devoid of Qa-m7. Significant increases in both the proportion of Qa-m7-positive myeloid cells and the level of Qa-m7 antigen expression have been observed in bone marrow cells regenerating after the administration of the cytotoxic agent 5-fluorouracil (5-FU). By exploiting this increase in Qa-m7 antigen expression during regeneration and the HPP-CFC-sparing properties of 5-FU, we have been able to enrich HPP-CFC from marrows 8 days post-5-FU treatment (FU8d) to purities of greater than 20%. Furthermore, discontinuous gradient centrifugation and fluorescence-activated cell sorting of FU8d bone marrow cells on the basis of their light-scattering properties and Qa-m7 expression has unmasked a further subset of HPP-CFC which strictly requires the combined stimulus of three hemopoietic growth factors (H-1, IL 3, and CSF-1) for clonal growth. These highly enriched subsets of HPP-CFC are either identical to or co-fractionate with transplantable multipotential hemopoietic progenitors capable of reconstituting the hemopoietic system of lethally irradiated mice. Up to one in three cells in these highly enriched fractions is an HPP-CFC, and up to one in two cells may be CFU-S assayed 13 days post-transplantation. In addition, these fractions contain progenitors capable of reconstituting the platelet, erythroid, and myeloid compartments of the marrow.     

Serological detection of B-cell ("Ia-like") antigens in serum of normal donor and in some sera of leukaemic patients

Some sera from normal donors (1/18) and from leukaemic patients (2/7 with acute myeloid leukaemia [AML], 1/4 with chronic lymphatic leukaemia [CLL], 0/3 with acute lymphoblastic leukaemia [ALL]; with high numbers of leukaemic cells expressing Ia-like p28,33 antigen on the leukaemic cell surface) inhibited the complement mediated cytotoxic activity of highly specific xenogenous anti Ia-like sera (which were prepared by immunization of rabbits with insoluble membrane fractions of B-type lymphoid lines) at a titre 1:4 or less. This effect was not observed with antisera directed against other membrane marker determinants (e.g. T lymphocyte specific antigens). These results suggest that at least a small proportion of membrane bound Ia-like antigens can be released from cell surfaces and in some patients these Ia-like moieties are detectable (by sensitive inhibition assays) in the serum.     

Differential effect of interferon on the expression of tumor-associated antigens and histocompatibility antigens on human melanoma cells: relationship to susceptibility to immune lysis mediated by monoclonal antibodies

Incubation of cultured human melanoma cells with human leukocyte interferon did not change the expression of melanoma-associated antigens (MAA) recognized by monoclonal antibodies and of Ia-like antigens but significantly increased the expression of HLA-A,B antigens and of beta 2-microglobulin (beta 2-mu). The effect is dependent on the dose of interferon and on the incubation time. Interferon-treated melanoma cells showed an increased susceptibility to lysis mediated by monoclonal antibodies to HLA-A,B antigens and to human beta 2-mu; on the other hand, interferon-treated melanoma cells did not change in their susceptibility to murine natural killer (NK) cell lysis and to immune lysis mediated by monoclonal antibodies to MAA and to Ia-like antigens, and they displayed a reduced susceptibility to human NK cell lysis. Therefore, the increased susceptibility of interferon-treated melanoma cells to lysis mediated by anti HLA-A,B and anti beta 2-mu monoclonal antibodies is likely to reflect the increase in cell surface expression of the corresponding antigens.     

Immunochemical and functional analysis of Ia-like antigens on human monocyte-macrophages with monoclonal antibodies

The distribution, structural profile and functional properties of Ia-like antigens synthesized by human monocyte-macrophages have been analyzed using monoclonal antibodies to common determinants of these antigens. Up to 45 and 70%- of monocyte-macrophages isolated from the fluid of blisters induced with cantharidin and from peripheral blood, respectively, react with monoclonal antibodies to human Ia-like antigens. The level of Ia-like antigens on monocytes-macrophages appears to be similar to that on cultured B lymphoid cells. Monoclonal antibodies to common determinants of Ia-like antigens specifically block antigen presentation by monocyte-macrophages to T lymphocytes as well as proliferative response of T lymphocytes to autologous and allogeneic monocytes-macrophages. These results indicate that common determinants of Ia-like antigens play a role in the interaction of monocytes-macrophages with T lymphocytes.     

Isolation of a human stromal cell strain secreting hemopoietic growth factors

A diploid fibroblastoid cell strain, termed "ST-1," has been established from a long-term liquid culture of human fetal liver cells. ST-1 cells are nonphagocytic, nonspecific esterase negative and do not possess factor VIII-related antigen but stain with antibodies specific for fibronectin and type I collagen. The ST-1 cells produce nondialyzable hemopoietic growth factors capable of stimulating the development of erythroid bursts, mixed granulocyte-macrophage colonies, pure granulocyte colonies, and pure macrophage colonies. These factors are active on both human fetal liver and human adult bone marrow progenitors. When liquid cultures of human fetal liver hemopoietic progenitors are established with a preformed monolayer of ST-1 cells, the yields of nonadherent cells, erythroid progenitors, and myeloid progenitors are greatly increased. These studies demonstrate that the fibroblastoid ST-1 cells support hemopoiesis in vitro and may be a critical element in the stromal microenviroment in vivo.     

Antiviral activity and anergy of gammadeltaT lymphocytes in cord blood and immuno-compromised host.

Gammadelta T lymphocytes recognize nonpeptidic microbial antigens without MHC restriction and display both lytic and proliferative responses to human immunodeficiency virus (HIV)-infected cells. This innate recognition involves both T Cell Receptor (TCR) and NK-receptor mediated signalling through non-peptidic metabolites and HLA class I down-regulation. We observed that HLA-masking and nonpeptidic phosphoantigens induce the expression of CD25 and CD69 activation markers on the surface of gammadelta T cells. Interestingly, CD94+ cell depletion by magnetic beads showed that the expression of this antigen is essential for Vdelta2 T cell activation by HLA-masking. Moreover, both phosphoantigen-stimulation and in vitro HIV infection resulted in marked Vgamma9Vdelta2 T cell expansion, whereas HLA-masking was unable to induce proliferative responses. Finally, we observed a relevant hyporesponsiveness to non-peptidic antigens in HIV-infected persons and in cord blood cells from healthy donors when compared to adult PBMC from uninfected donors. Altogether, the reduced ability to naturally recognize the infected cells may contribute to HIV-disease progression and may facilitate maternal transmission of HIV infections.     

Expression of 18.6/CD23 Antigen on Human Lymphoid Progenitor Cell Lines and Phorbol 12-Myristate 13-Acetate (PMA)-Induced Microglia-Shaped Cells

The nature of lymphoid progenitors and factor(s) determining commitment to either the T- or B-lymphocyte pathway are poorly understood in the human system. In this study, we generated a monoclonal antibody (MoAb), 18.6, that recognizes a cell surface antigen on a human lymphoid progenitor cell line (FL4.4). MoAb 18.6 reacted with lymphoid progenitor lines, B lymphoid cell lines, and myelomonocytic cell lines. It did not react with any T cell or erythroid leukemic cell lines. Two color FACS analyses of normal lymphoid tissues showed that MoAb 18.6 reacted with a majority of CD20⁺ mature B cells and a minority of CD64⁺ monocytes. Molecules of 3 different sizes with MW of 34, 45, and 68 Kd were precipitated with MoAb 18.6 from the lymphoid progenitor cell line. The 18.6 antigen was not expressed on a fetal liver-derived lymphoid progenitor-like cell line, FL1.4, which has the capacity to differentiate into microglia-shaped cells upon PMA-stimulation. Stimulation of FL1.4 cells with PMA induced expression of the 18.6 antigen within 24 hr and the microglia-shaped cells stained positively with MoAb 18.6. Finally, cloning of a cDNA that encoded the 18.6 antigen revealed that the 18.6 antigen is identical to the CD23 antigen. Taken together, these data suggest that the 18.6/CD23 antigen is expressed on lymphoid precursors at a very early stage of differentiation.     

Variation of HLA-ABC surface antigen expression on adenocarcinoma of the colon in correlation with the degree of differentiation

The expression of HLA class I antigens was tested on biopsy specimens originating from 90 patients suffering from adenocarcinoma of the colon. Three different samples were examined from each specimen: one from the tumor and the other two from the neighboring surrounding surgical margins. Twenty-seven out of 27 well-differentiated carcinomas were found highly positive for the presence of HLA class I antigens. Most of the moderately well differentiated tumors (37 out of 46) were weakly positive. None of the poorly differentiated tumors (n = 11) nor the mucin-producing tumors (n = 6) expressed HLA class I antigens. In 180 histologically normal colonic epithelia from patients suffering from adenocarcinoma of the colon (surgical edges free from tumorous tissue of the same specimens) no positive expressions were found. These results tend to suggest that class I HLA-ABC deficient, poorly differentiated tumors may possibly evade lethal immune aggression by HLA-restricted cytotoxic T cells and thus progress to overt malignancy. This negative expression may provide an explanation for the poorer prognosis observed among patients afflicted by a poorly differentiated adenocarcinoma or mucin-producing adenocarcinoma of the colon. Furthermore, these results tend to suggest that enhanced expression of HLA class I antigens on colonic epithelium could serve as a clinical laboratory indication for further examination looking for the possible emergence of neoplasm. If further verified, this may prove to serve as a predictive diagnostic tool for screening populations at risk.