Selective loss of CD4+ CD45R+ T cells in peripheral blood of multiple myeloma patients

Abstract

The phenotypic distribution of T-lymphocyte subsets in peripheral blood from multiple myeloma (MM) patients shows a reduced proportion of CD4+ cells and a normal proportion of CD8+ cells. The decrease in CD4+ cells could be due to a random process, with all types of CD4+ cells being equally affected, or it could reflect a nonrandom process with selected subsets preferentially reduced. In order to distinguish between these possibilities, double immunofluorescence analysis was performed on blood samples from patients with MM, patients with monoclonal gammopathy of unknown significance (MGUS), and age-matched normal donors, using monoclonal anti-CD4 or anti-CD8 paired with antibodies to the common leukocyte marker Lp220 (CD45R) or 4B4 (CDw29). Normal peripheral blood lymphocytes (PBL) include two phenotypically and functionally distinct CD4+-cell subsets, identified as CD4+ Lp220+ 4B4- and CD4+ Lp220-4B4+, whereas the majority of CD8+ cells expresses Lp220 (70-85%). MM patients had a highly significant selective reduction of the CD4+ Lp220+ subset compared with normal controls (P less than 0.001). Although the percentage of CD4+ Lp220- cells was also reduced in some MM patients relative to normal donors, most of MM patients had an elevated Lp220-/Lp220+ ratio of CD4+ cells (P less than 0.001). The proportion of the two CD8+ subsets was also markedly abnormal. In the set of patients studied the abnormalities within the CD4+ and CD8+ lymphocytes were exclusive to patients with MM since patients with MGUS had normal proportion of CD4+ and CD8+ subsets.

Cell proliferation and cytokine production by CD4+ cells from old mice

“…These findings are consistent with previous reports by us [231 and others [14,221, with the exception that greater increases in 6C10h' cells in older Balb/c mice were noted in one study [14]. In the human system, numbers of CD45RBl" and CD2gh' T cells are elevated in elderly individuals [21,24,47]. In both species, these alterations in the phenotypic makeup of the CD4' cell pool appear to occur gradually with age [21][22][23][24]471.…”

“…CD4' cells were cultured in the presence of accessory cells derived from young mice, and were stimulated with 2C11 s or 2C11 i. At 24,48, and 72 h of culture, cells were assayed for I3HITdR uptake and supernatants were assayed for IL-2 (CTLL.6 assay) and (1 1.6 assay) content. The data represent the peak response for each group.…”

T cells in myeloma

“…3 The depression of the CD4/8 ratio is usually more obvious in patients with progressive disease. [4][5][6] It has been reported that within the CD4 þ T cell compartment, there is a selective loss of cells in the naive CD4 þ CD45R þ subset, 7,8 suggesting an enrichment of memory CD4 þ cells and a failure in the differentiation pathway to give rise to new naive CD4 þ T cells. 8 Conversely, in patients with myeloma at diagnosis, a reduction in total and activated CD4 þ T cells but not naive CD4 subsets has also been reported.…”

The prognostic significance of T cell receptor β gene rearrangements and idiotype-reactive T cells in multiple myeloma

“…Samples were collected at all stages of the disease patients with myeloma can have an altered CD4:CD8 ratio including presentation (n = 35), plateau/stable phase (n = 39) which is related to a decrease in naive CD4 cells in advanced and progressive disease (n = 45). Patients were treated accordstages of the disease, 11,12 an increased number of large granuing to the ALSG myeloma trial protocol which involved multilar lymphocytes and activated T cells 10,13,14 and a sensitivity agent therapy (prednisone, cyclophosphamide, doxorubicin and bis-chloronitrosourea) plus or minus alpha-interferon. 29 Patients over 70 years were treated with melphalan and receptor ␤ probe used was a 0.4 kb fragment derived from a cDNA which includes the T cell receptor CT␤2 region of light chain disease (one and one ) were used to purify IgG and light chains, respectively.…”