Increased expression of T cell antigens on T cells in classical Hodgkin lymphoma

Abstract

We read the work by Seegmiller et al. (1) with interest regarding the increased expression of CD7 on reactive T cells in classical Hodgkin lymphoma (CHL). We had also observed an increase in CD7 in conjunction with increased CD45 expression on a subset of CD4þ T cells in lymph nodes involved by CHL (Fig. 1), raising the question whether the expression levels of other T-cell associated antigens might also be altered in CHL. To further examine this finding, T cell populations were retrospectively evaluated in 50 lymph nodes involved by CHL and 50 reactive lymph nodes. The immunophenotypes of CD4þ and CD8þ T cells were quantitatively evaluated by normalizing the expression of a given antigen to a reference population (non-T cell lymphocytes). The normalized ratio was calculated as the median fluorescence intensity (MFI) of the CD4þ or CD8þ T cells for a given antigen divided by the MFI of the reference lymphocytes for that antigen. Statistically significant (P < 0.05, measured by student’s t test) increased expression of CD2, CD5, CD7, and CD45 on the CD4þ T cells and CD5 and CD45 on the CD8þ T cells were demonstrated when T cells from lymph nodes involved by CHL and reactive (nonneoplastic) lymphadenopathies were compared (Fig. 2). Both the CD4þ and CD8þ T cells from CHL demonstrated statistically significant decreased expression of CD3 when compared to reactive lymphadenopathies. Next, we evaluated lymph nodes specimens for increased expression of CD7 and CD45 on CD4þ T cells in five patients who had multiple tissue biopsies (evaluated by both flow cytometry and morphology). Each patient had at least one biopsy without evidence of lymphoma and one biopsy involved by CHL, yielding a total of 8 reactive and 10 CHL-involved lymph nodes studied. All the lymph nodes involved by CHL showed CD4þ T cells with increased CD7 and CD45, while none of the reactive lymph nodes showed this finding. This result suggests the reactive CD4þ, increased CD7þ and CD45þ T cell population is present only in lymph nodes involved by CHL but not globally in all the tissues from CHL patients in the absence of the neoplastic population. The inference is that the microenvironment (possibly mediated chemokines) is responsible for the induction of this population. In clinical practice, this reactive CD4þ T cell population in CHL can be readily identified on a plot of CD45 vs. CD7 (Fig. 1), provides support for the diagnosis of CHL, and serves a screening tool to prompt further definitive evaluation for the neoplastic Hodgkin and ReedSternberg cells of CHL by flow cytometry (2,3) or immunohistochemistry (4). Studies are underway in our laboratory to determine the biological significance of this reactive T cell population.